Staying Connected

     All of our cells can talk to each other though the junctions of “windows” and “doors” (receptor junctions) that exist between them.  When communities of billions of cells are all connected integrally together, unified and united by the integrated signaling networks branching through all of the junctions between them, not only are the cells balanced, alive, and happy but they are amazingly powerful.

   To give you just a small idea at the vast potential of cells in a network of connecting junctions, let us briefly consider the most complex and powerful cell network we know: our own human brain.  The brain consists of an enormous network of interconnected brain cells.  Each brain cell comes into contact with several of its neighboring brain cells through a series of interconnecting “wires” (called axons).  There are junctions that exist between the axons of the brain cells (called synapses) where the signals from one brain cell hop over to the next one.  It turns out that our memories, our associative powers, our cognitive abilities, and mostly all of the functions in our brain are actually found in the tiny synaptic junctions that connect our brain cells.  Is this not incredible?

   Scientists have found that synaptic junctions between brain cells can be “programmed”.  The brain cells determine how many “trigger” molecules to put in each of the synaptic junctions.  Depending on the number of trigger molecules in the junctions, the strength of the electrical signal that makes it across the junction to the next brain cell is determined.  While traveling across the various junctions, the signals can be stopped, passed along, or even amplified, as determined by this trigger programming.  Our thoughts and memories are most likely stored in the pattern of pathways that electrical messengers follow through the brain. And these signal pathways are determined by the programming in the junctions.

     If you were to allow your mind to wander back to your childhood home for a moment, you might remember what your house looked like; patterns of the porch, the yard, familiar rooms, and surroundings might flood into your head, accompanied perhaps by memories of the sights and smells of home.  Images of these familiar patterns are almost always associated with the way we felt; feelings of safety, warmth, or anxiety related to events that took place there.  At every moment, the endless variety of patterns that pervade our surroundings are almost instantly associated in our mind to our current location in our mind’s map and our current emotional condition.  Without this ability, we would literally be lost and clueless.

     Perhaps the very secret to our intelligence lies in the amazing power that our mind has of building associations to the limitless variety patterns that surround us.  At this moment, your mind is associating the patterns of letters in the words you are reading on this page with the concepts they represent.  Different shapes and patterns almost naturally are associated with each other.  The written symbol “Tree” invokes a certain pattern in our mind.   We can hardly help it.  It is just the way it is.  Our language, both written and verbal, depends on this power of association.

     If such an amazing organ as our brain–capable of embodying almost unlimited powers of association– is built by a network of electrical and chemical messenger pathways connected together by programmable junctions, then can you imagine the possibilities when all of the trillions of cells in your body are connected together by similar networks of signaling pathways? Just like your brain cells, all the cells in your body have similar junctions where signals are passed between them.  The real “brain power” of all our cells is found in the programming of these junctions.  These signaling junctions exist between every cell.  Understanding the programming options available at the “doors” and “windows” of the cells leads us to discover the real software that determines how the whole of our body functions.  Can you imagine the complexity and power when trillions of cells connected together in a huge signaling network?  Actually, yes, you can imagine it.  You live in it.  It is your body!

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Life is Wonderful!

111712-Life-Is-Wonderful    

As we have begun to consider what it must be like to live in the enormous communities of cells that make up the tissues and systems of our body, and all of the marvelous amounts of interactions that are taking place inside and between the cells, let us pause for a minute and think of how good life can be.

Life is good when…

    There is integrity – everything is functioning the way it needs to make it work

    There is understanding – all of the individual members hear and respond to the needs of the others

    There is abundance – all individuals have everything they need at the time they need it

    There is balance – there is a way to efficiently resolve stress and regain balance when things go wrong

    There is unity – a clear vision of what needs to be accomplished for it all to work out

If you can recall a time when life was wonderful, there might be a few other items that come to your mind.  You might have had a time when you were able to be heard and you were able to hear and respond to someone, a time when communications were clear and just a glance conveyed volumes, a time when meaningful connections made a difference, a time when you were the best you could be.  You might have said, at such a time, that you felt “alive”.

     Isn’t it interesting that in the moments of life that make you feel the most alive you are surrounded by others that are interacting with you in a meaningful way.  There is expression, communication, interaction.  These elements are always present in the good life.  They seem to be at the very essence of life.

     Your cells also feel the same way you do.  When they have the good life, they are smiling at us when we look at them through the microscope.  Expression, communication, interaction have the same importance and effect on cells as they do on us.  The signaling pathways that allow cells to talk to one another make all the difference.  The way that your cells interact make them part of YOU, and give them the role they play inside you.  If our cells are happy, we are healthy.  The better and clearer the signals are between cells, the better chance they have to keep happy and healthy. 

       If we are to have the good life, it would be wise to learn a few lessons from our cells. 

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A Look at the Redox Signaling World

For 50 years, we brutishly held onto the belief that the oxidants served absolutely no good purpose and were unnecessary harmful byproducts of our metabolism.  Based on brilliant work done by Dr. Britton Chance (a renowned biophysicist, pioneer in medical instrumentation, and Olympic gold medalist), we first started to realize that oxidants and free radicals are not all inherently harmful and perform fundamental signaling roles in the body that are essential to sustaining life. Now, some 30 years later, it is patently clear that these types of oxidants play an absolutely essential role in the redox signaling networks that initiate healing throughout all of our cells and tissues.  We now see that redox signaling originates where there is cellular damage, creating a disturbance in the balance of oxidants and reductants (sending smoke signals) and such signals cascade through various pathways that deliver the messages to the necessary responders that can fix the damage and reestablish the needed redox balance.  Without these redox signaling networks, healing would literally be impossible.

As the field of redox signaling advances, we have found that up to about the age of 10-years-old these healing pathways work extremely well; healing and immune response is quick and accurate, and redox signaling pathways are at peak efficiency.  We have also realized that over the years, the mitochondria– the hubs of the redox signaling networks– gradually degrade over time.  Mitochondrial furnaces are the origin and source of oxidants in the redox signaling networks. As such, they take the brunt of the oxidative damage (for much the same reason that the “fireplaces” in our homes incur the most damage from “smoke”).  This process of gradual mitochondrial degradation in our cells can occur over decades and is now recognized as one of the major causes of aging.

As the mitochondria fail to function optimally, there is less ATP fuel available to carry on the orchestration of life and to make necessary repairs.  To add insult to injury, the production and regulation of the redox signaling molecules are also diminished. The redox signals that mark the cellular problems are not as persistent or strong (it is difficult to locate a forest fire in a “burnt out forest”).  As a result, healing is slower and less accurate, and immune response is also more sluggish and less accurate.  By the time we are 80-years-old, average mitochondrial efficiency has decreased by 70%.  There comes a time when the cells and tissues are simply not able to repair and replace themselves as fast as they are becoming damaged by buildup of oxidative stress and garbage.  At this point, damage propagates quickly; we age rapidly and eventually die.  Accumulated, unresolved cellular damage is the basis behind all of the current theories on aging.  In fact, unresolved cellular damage is at the core of every known disease.  If we could only find a way to facilitate more efficient repair of cellular damage; then cell damage could be repaired faster than it occurs and we would be able to have eternal health and youth.  It is not clear if this is even possible, but any possible fountain of youth would certainly involve making the redox signaling pathways more efficient.

The field of redox signaling is destined to become the field of science that will fuel the greatest medical discoveries in this next century and beyond.  The universal signaling systems that exist in the fluids of life, inside every living cell and tissue, the signaling systems that have existed from the inception of life and in all forms of life that have existed or will exist on earth constitute the most fundamental signaling systems in biology.  They reveal to us what makes life work on the smallest, most universal level.  Redox signaling describes the molecular signaling mechanisms that modify the structure of water, that transmit messages throughout the fundamental fluids of life.  The simple, common molecules that initiate and transmit these messages through living fluids are mostly manufactured from water (hydrogen and oxygen) and salt (chloride and sodium), and also include a few of most common elements of life (carbon and sulfur).  These are the molecules that initiate and mediate the life-sustaining redox signaling pathways throughout all of the cells and tissues of our body.

Here is a current listing of these molecules for reference:

 

Redox Signaling Molecule Chemical Symbol Major Sources Lifetime (half-life) in Cells : Tissues
Superoxide Free Radical O2*- Mitochondria, NADPH Complexes 15 millionths of a second : 10 thousandths of a second
Hydroperoxyl Free Radical HO2* Mitochondria, NADPH Complexes 60 millionths of a second : 30 thousandths of a second
Hydroxyl Free Radical HO*- Fenton Reaction, H2O2 1 millionth of a second
Hydrogen Peroxide H2O2 O2*- 20 thousanths of a second :  10 seconds
Nitric Oxide Free Radical NO* NOS, NADPH 0.5 seconds : 4 seconds
Hypochlorite ion OCl- MPO 1 – 10 minutes
Hypochlorous acid HOCl MPO, acid 30 seconds
Hydrogen Sulfide H2S CysBSynthase, Sulfides ?
Singlet Oxygen 1O2 O2*-, Mitochondria ?
Carbon Monoxide CO Environment, HO minutes

 

If you are interested in looking up scientific literature in the field of redox signaling, you probably will not find any direct reference under the name of “redox signaling molecules”.  I have taken some literary license to create descriptive names– such as “semaphores”, “reductants” and “redox signaling molecules”– that are not commonly used in scientific literature to describe such classifications of molecules. I have attempted to define these literary terms and place the scientific names in parenthesis as much as possible.  In order to do literature searches on this group of “redox signaling molecules”, try looking up:  Reactive Oxygen Species (ROS), referring to the species of molecules containing oxygen (hydrogen peroxide, superoxide free radical, hypochlorite ion, singlet oxygen).  Reactive Nitrogen Species (RNS) refers to species containing nitrogen (Nitric Oxide free radicals and other downstream nitrogen radical cascades).  Of course, you can refer to each by its chemical name to get information. For example, google/scholar: “redox signaling hydrogen peroxide”.  If you wish to get information on “reductants”, it would be best to search under “electron donors” or “reduced species”.  The reduction pathways, often involving electron carriers, are difficult to find in the literature, mostly because they are not nearly as well documented as the oxidative pathways.  Following all the papers written by a specific author also can be instructive.  As usual, when dealing with a new emerging field of science, the names given new concepts are at times vague, non-unique, and are based on historical development, much like the terms oxidation and reduction themselves.  Finding descriptive, widely-adopted names for these new concepts is all just part of the challenges we encounter while traveling along the journey of discovery.  Much is to be gained by reading about the research on redox signaling. There are literally hundreds of scientific articles being written on this subject every month, representing thousands of months of scientific effort across the world.  It is truly marvelous to be living in this day and age where knowledge gained from everywhere in the world is almost instantaneously accessible by anyone with a true desire to know.

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The Heart of Redox Signaling Country

      We are now traveling directly through the middle of the beautiful flowing seascape of redox signaling country.  This country extends in all directions for miles, far beyond what it is possible for the eye to see.  We are just starting to see how far it goes.  We get the sense that redox signaling is a fundamental part of the communication networks that hold all of the cells inside our body into unified and thriving communities; communities of trillions of cells that comprise all the tissues that form all of the organs and systems of our body.  As we have traveled a while down the rivers of life (blood vessels) that supply these vast communities of cells, we have watched with fascination everywhere around us as cells are constantly becoming damaged, being repaired or taken down, dividing, and being rebuilt from the supplies found in the blood.  Messenger molecules are running around coordinating all of these construction efforts.  As we watch all the activity, we venture to enter into one of the cells along the way to explore a bit deeper what is going on inside.  We follow a sugar molecule (glucose) into one of the glucose doors (GLUT receptors) of one of the cells.  It really doesn’t matter which cell we pick, any cell will do.

     It is cozy inside the living cell, there are hundreds of fire places (mitochondria) where the sugar molecules are being burned (oxidized) to produce fuel.  About 90% of the oxygen we breathe goes into these mitochondria fireplaces.  We notice, as we have seen before, that redox signaling molecules (ROS such as hydrogen peroxide, superoxides, hypochlorites, etc.) are also billowing out of these fireplaces just like smoke comes out of fire.  As you can imagine, with hundreds of fireplaces in the cell there are quite a lot of these redox signaling ROS (smoke) being produced in the cell.  Recall that we explored this part before also.  We can see that the excess ROS molecules building up inside the cell are activating messengers (smoke detectors) that rush off to push genetic buttons that produce the cell’s master antioxidants [Glutathione Peroxidase (GPx), Superoxide Dismutase (SOD), and Catalase].  This super team of antioxidants is perfectly built by the cell to eliminate the ROS (smoke) in the cell.  They are stationed around the areas in the cell that can be damaged by ROS, such as the DNA databases and the mitochondria.  This super team of antioxidants are super effective in eliminating the ROS smoke in the cell.  Superoxide Dismutase (SOD) eliminates Superoxides, Catalase eliminates Hydrogen Peroxide and Glutathione Peroxidase (GPx) pretty much eliminates everything at the rate of about 70 million oxidant molecules per second.

     So far, inside the living cell, we have seen the mitochondrial fire places burning sugar to produce energy along with billowing clouds of redox signaling molecules (the ROS smoke) that contain oxidants.  We have also seen antioxidants stationed around the cell that effectively eliminate the ROS smoke, especially around sensitive parts of the cell.  This is the scene that scientists discovered 30 years ago.  Their assessment of the scene was that the oxidant smoke produced by the mitochondria is bad and the antioxidants that clean it up are good.  It seemed pretty obvious, “oxidants are bad, the antioxidants cleaning them up are good”.  The only problem with this viewpoint is that it is not entirely true.  In recent years it has been well established that these ROS oxidants are not only good, they are absolutely essential.  The reason for this becomes obvious when you consider what happens when the cell is damaged.

      Our tour of the inside of the cell is interrupted by a bacterium that attaches itself to the outside of the cell.  We can see that the bacterium starts to attack the cell by injecting digestive juices into the cell that begin wreaking havoc with the machinery inside the cell, including some of the fireplaces.  These damaged fire places don’t work very well, the fires go out and allow a large excess of ROS smoke to pour into the cell.  The “smoke detector” messengers now relay this condition to the DNA database.  The cell takes this signal very seriously and starts to flood the cell with repair molecules in order to fix the damage and to send distress messengers to the immune system.  In this scene, the ROS smoke plays a very important role.  It starts the signaling process necessary to repair the damaged cell and to call the immune system.  Without the ROS smoke, cells cannot activate the processes needed to repair themselves.  If there is too much damage done to the cell, this redox signaling process will eventually result in the cell dying, taking itself apart and recycling its parts.  These parts will be used as supplies to build a new cell when a healthy neighboring cell divides to take the place of the previously damaged cell.

     It now becomes clear to us that these redox signaling molecules (the ROS smoke) have been the signaling molecules all along that have been instrumental in ordering the repairs, instigating demolition of damaged cells, and causing the replacement of damaged cells – a process that we have seen all around us throughout our journey.  These redox signaling molecules stimulated the cells to detect internal damage, to order repairs, or cause the damaged cells to die and be replaced.  They are responsible for maintaining all of the healthy beautiful rows of well-maintained healthy cells we have seen everywhere around us on our journey. We can now see why these redox signaling molecules, ROS oxidants (smoke), are so important in our cell communities.

     Imagine what would happen in our body without these redox signaling molecules.  If the redox signaling molecules did not exist, if our mitochondria stopped producing them, then cell damage could not be detected, repairs would not be ordered, and damaged cells would not die or be replaced.  If a bacteria landed on a cell and started injecting digestive fluids, the cell could not order repair molecules, it could not send out a distress call to the immune system.  It would just sit there and “take it” and become more and more damaged over time.  If the damaged cell could not die and be replaced, then it would just sit there and become more and more beat-up over time until it stops functioning as it should.  Can you imagine what our cell communities would look like if that were to happen.

     Cancer cells and pre-cancerous cells, in fact, are our own damaged cells that cannot be detected.  They cannot repair themselves or be replaced and they certainly do not function as they should.  It is not surprising, then, that we found that in cancer cells the mitochondrial fire places have been shut down and thus their production of redox signaling molecules has been shut down.  Without redox signaling processes, cancer cells cannot be detected, they cannot order repairs, and they cannot die.  If they lose their ability to interpret the signal to stop dividing and continue to multiply then they become malignant tumors that can grow without restraints.  Scientists have given rats mega-doses of Intravenous vitamin C (an antioxidant) to see what would happen if they removed much of the oxidants (ROS smoke) from the cells of the animals.  With high doses of antioxidants, these animals developed cancers, infections, diabetes, and died early in morbid conditions.  This was a clue that started the scientists on the journey to discover the importance of this ROS smoke (later known as redox signaling molecules).  We now know that ROS is universally and fundamentally important for all types of cells in all forms of life on earth.

      We emerge from the cell much better informed and look around.  We see beautiful rows of well-maintained cells stretching outward in all directions.  We see constant construction projects, cells being taken down, repaired, cells being duplicated and rebuilt all around us.  In the back of our mind we think, thank heavens for redox signaling.

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How to Build a Heart (or any other organ)

      heart stem cell      Last week, we explored a simple picture of what is necessary to build a cell.  We saw that only a few varieties of raw materials are needed by the cell (including nutrients, amino acids, energy, salt water and oxygen).  The DNA plans found in the nucleus and a properly organized work force with messengers then go about building the cell and staffing it.  Although there is incredible complexity in how all of the pieces of a cell are assembled, once a living cell is assembled, it is not difficult to duplicate.  In fact living cells will automatically duplicate themselves by copying their DNA and dividing, building two similar cells from the materials found in one of them and they won’t stop dividing until they encounter cell neighbors that tell them to stop or they run out of raw materials.  It might be surprising to some people that the cells inside us can live outside of our body.  Scientists can take most any type of cells out of our body and grow them in a glass dish.  As long as they are supplied with sufficient raw materials and messenger molecules, they will continue to grow in the dish.  There are many samples of living cells from people who have died more than 50 years ago.  It makes you wonder, if we were smart enough to feed our own cells the raw materials and nutrients they need, our cells would be much stronger and last much longer.

      The most interesting question to ask now is, what exactly determines the kind of cell (skin cell, muscle cell, brain cell, etc.) that is being built?  The answer is not found solely in the DNA.  Keep in mind that every single cell inside us has the complete DNA instructions to build any other kind of cell in our body.  The marvelous mystery of how we are all put together with all of the thousands of different types of cells in our body is found in the signaling molecules and messengers surrounding our cells that are being passed around between and inside our cells.  What does this mean? It means that every cell in our body is built the way it is and works as it should because of the messengers in the environment where it lives.  If a cell lives in the heart, it works like a heart cell because of the messengers passed around from neighboring heart cells.  If a cell lives in the brain, it works like a brain cell, again, because of the messengers passed around in the neighborhood where it lives.  Can I ask the crazy question, does that mean if I took a brain cell out of the brain neighborhood and placed it into the heart neighborhood, would it somehow listen to the surrounding messengers and transform into a working heart cell?  It sounds a bit like science fiction.  The answer is surprising and alluring.

     There are cells in your body, called “stem cells” (produced in different areas of the body, like the stomach fat) that do transform into any type of cells they attach to.  So if a stem cell attaches in the heart, it will build itself into a heart cell.  If it attaches to the brain, it will build itself into a brain cell.  Once stem cells have transformed, however, they are “locked in”.  Say stem cells attached to the heart and have transformed into heart cells, these cells themselves start to produce the messengers found in the heart cells in their neighborhood.  This sort of “locks them in” to being heart cells in the neighborhood they are in by the “heart cell” messengers they themselves start producing.

     The incredible ability of stem cells to transform has been proven thousands of times over.  Scientists have taken stem cells out of the body and grown them in dishes.  They then have divided the same identical stem cells into three separate dishes.  In the first dish, along with the nutrient broth, they placed the molecular messengers found in kidney cells, in the second dish those in liver cells, and the third those in heart cells.  The cells in the first dish became kidney cells, the second dish liver cells, and the third, of course, heart cells.  And we have not even started to enter the “rabbit hole” yet.  This gets deeper and more interesting and stranger the deeper we go.  We have found that just by placing stem cells together in communication with other cells they start to assemble and build themselves into complete tissues, with blood vessels, tubes and layers, and all other types of cells needed in the neighborhoods to recreate the living tissue.  On the internet you can see videos where whole working kidneys are “printed out” by 3-D printers that just spray out layers of certain types of cells found in kidneys.  In hours these cells start to self-assemble into the incredible complexity of a working kidney that can even start to filter blood and produce urine.  From the messengers they are passing back and forth, cells can transform into exactly the types of cells needed in the place where they are to produce all of the living tissues needed in the neighborhood where they live.  Single cells have the ability to assemble whole neighborhoods of cells and tissues.  Scientists have even cloned a whole animal (remember Dolly the sheep) by placing DNA from a skin cell inside an Egg cell.  The transplanted DNA started reacting to the messengers inside the egg cell.  The cell transformed into a viable Egg cell and started dividing to produce the developing fetus of a whole animal.  The ability of a single cell is absolutely incredible.  This ability comes from the ability of the internal workings and DNA of the cell to read and respond to environmental messengers.  I suppose you can say that a cell is what it eats, literally.

     Right now, scientists are creating working organs in laboratories that may even have the potential to rebuild or replace deficient organs with new organs or tissues built in the laboratory, or in our bodies using stem cells.  The picture on the top of this post is of a living functioning rat heart self-assembled by rat stem cells placed on a heart frame.  After a few days, the heart self-assembled from a bunch of stem cells and even started beating.  The possibilities are endless.

      A side note: as we study the fascinating dynamics of our cell communities as they build themselves, we also have learned that besides the messengers being passed around that determine what our cells become, our cells are also programmed to respond to what we eat.  What we eat literally changes the type of cells we have and how they work.  Our body are made to break down the nutrients found in raw plants and meats in our environment and convert them into the molecules our cells need to thrive.  Anything more or less than this can severely stress our cells and systems.  More than anything else, what we eat makes a difference.  Did you know that even our DNA changes with our environment?  We have molecular machines inside our cells that integrate genetic material found in our environment and graft them into our own DNA.  It should not be so surprising, this is how viruses work.  Viruses contain genetic material that are integrated into the DNA of infected cells that codes to produce more viruses of the same sort.  Snippets of DNA are readily shared between cells and may comprise some of the messengers that we have been considering that change the function of our cells based on the environment in the neighborhood where they exist.  All of this knowledge can work together for our benefit.  Think of the possibilities, heed the warnings we feel in our hearts.  Life is truly beautiful.heart stem cell

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How to Build a Cell

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While we are in the underwater world of living cells inside us, it becomes obvious that there is quite a bit of construction going on all around us.  Communities of billions of cells houses are being taken down and rebuilt every day;  equivalent in scope to the demolition and rebuilding of every building on earth, every day.  What does our body need to build and rebuild our cells?

Building Materials — Micronutrients (vitamins and minerals, molecules taken from our food), fuel (sugars and fats), amino acids (the building blocks for proteins).  All of these molecular materials are found in plants, you can build an elephant from just the materials found in plants.

Water and electrolytes [salts] — A nice high water table helps everything work smoother, a low water table slows everything down.

Oxygen — This hardly needs mentioning.  Let’s point out, however, that oxygen is only one of the many oxidants that are essential to the function of our cells.

Building Plans — The building plans for the cell are found in the DNA.  In the DNA there is a repository of all the plans needed to build the micro machines, workers, and structures in the cell.

Messengers — These are the signaling molecules that run back and forth delivering messages to the workers.  They read the DNA plans, push the genetic buttons that create the workers and machines, and deliver the messages that tell the workers what to do.

Is there anything else needed?  I think we have listed everything we need to build a cell.  Out of these components, which one do you find most interesting?

In the last 15 years almost all of the groundbreaking work in cellular microbiology has been done on the messenger components of the cell, affording the scientists several Nobel Prizes.  Redox signaling messengers (made from the most abundant elements in nature) are perhaps the most fundamental of all the messengers in the cell.  They pass the messages needed to build and maintain all the types of cells that exist in nature.  There is no doubt that understanding the messenger systems of the cell will bring us the next greatest discoveries in life sciences.

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Redox Signaling Country

cropped-lake_02.jpgWe are finally descending into the heart of redox signaling country, we come to a place where there are many different pathways branching off in many different directions.  And it looks like we are going to get wet.  All of these redox signaling pathways are going directly into a huge ocean of salt water.  We put on our scuba gear and tread in.  There is no other way.  All molecular activities in all forms of life on earth take place in salt water, it is the vital fluid of all life.  All our cells and tissues are submersed in this ocean of fluids.

Under the salt water we find great currents of vital elements moving past in living rivers coursing throughout the extensive communities of living cells.  Each cell is like a submerged house in this vast ocean, all of the cells are stacked in neighborhoods closely surrounded by these flowing rivers of currents; like houses along streets.  These communities of cells are connected and fed by the currents that flow past them. Every living cell is alongside these moving rivers of life; each cell is connected by it.

Now imagine, if you can, this underwater community extends to fill all the oceans on earth, some 70 trillion houses; equivalent to every man, woman and child on earth today, each building 10,000 houses along these river currents.  This represents the vast extent of the community of cells that exists inside just one living human being.

Of course, the rivers of life are mostly the networks of blood vessels–literally miles of them–feeding all the cells in our body.  Our heart pumps this river of life though this vast network of blood vessels that connects and supplies our cells with all of the elements of life that they need.  This river travels in only one direction, nothing much travels upstream.  Along with oxygen, all of the fuel, building materials, chemical signals–everything needed to sustain life–travel along these rivers.  The things that cannot be transported directly through the plasma fluid in the veins (for whatever reason) have little specialized “submarines” built for them to transport them down this river of life.

The cells have access to these currents of life through the receptor windows, chimneys, vents and doors.  We can imagine the little molecular inhabitants of these cell houses floating in these fluids, swimming around inside their houses and between their houses under the water.  The fluid that exists inside and around our cells in our body is somewhat similar to the seawater that is in our oceans.  Blood plasma contains 0.9% salt, with a mixture of minerals; the ocean contains 1.9% salt, with similar types of minerals.  We are now getting a better idea of what it really must be like to live in a community of cells.

With this picture in mind, it is easy to see that the fluid pathways that exist in, around and between our cells (individually and collectively) allow the molecules that are needed to sustain life (fuel, material, supplies or signals) to be available to all of our cells.  It is also important to know that each living cell controls access to the “doors” and “windows”, and will not allow entry to just any molecule that happens to be floating by.  In our cell communities, the doors and windows are called receptors and co-receptors and they selectively allow in only the fuels, materials supplies, and signals that are needed and used by the cells at any particular moment. Very few things can “seep through the cracks”.  In this way, the cells have control over what is allowed to come in and what is allowed to go out.  This selective behavior of the cells makes sense as we consider the complex logistics necessary for sharing resources among the trillions of cells in this thriving underwater community.  Collectively, all of the fluid pathways constitute a vital one-way river of life that connects, surrounds, and passes through all of the cells, tissues, organs and systems of our body.

Another experience in this underwater world becomes very real to us.  We cannot communicate with each other except by finding a way to send messages through the salt water that surrounds us.  Since we have eyes, it may be easier for us to use lights or hand signals; but the molecular inhabitants of this world must have different, more interesting ways of communicating among themselves.  In order to send a signal through water, the inhabitants have a limited number of options. If they have excess electrons or protons, they can use “email” and send electrical signals along the cables that connect the cells (neuronal material).  If not, molecules can physically move with the currents between houses and travel like mail carriers to deliver the messages personally to the intended recipients (like hormones).  Or, more interestingly, they can modify the molecules in the surrounding water (by reducing or oxidizing them) to and send ripple-like messaging to other nearby molecules through the surrounding salt-water medium.

Let us try to understand how this last form of communication works.  How can life’s molecules modify the salt water molecules that surrounds them?  We discover that as with all molecules, salt-water molecules can be reduced and oxidized (redox’d) through exchanges of electrons.  Some biological molecules, like NADPH complexes, physically modify salt-water molecules (Na+, Cl, H2O) and reorganize them into other molecules such as hydrogen peroxide (H2O2), super oxides (O2*-,HO2), hyperchlorites (OCl-, HOCl, NaOCl), captured gasses (O2, H2), ions (H+,OH), and a variety of other molecules, ions and free radicals.  These molecules are part of the class of redox signaling molecules that can send messages through the salt water.  If you are curious to find a complete list, you can google Reactive Oxygen Species (ROS) and find all in this class of molecules.  ROS are part of the fundamental class of redox signaling molecules found in all living organisms.  There are other types of redox signaling molecules.  If you add nitrogen (N2), which comprises 80% of the air we breathe, then nitric oxide (NO) can be formed, this is part of a class called Reactive Nitrogen Species (RNS).  Then adding sulfur, very abundant in sea water, we also get Reactive Sulfur Species (RSS).  ROS, RNS, and RSS comprise the class of redox signaling molecules that we are exploring.  Each one of these redox signaling molecules can carry clear messages through the salt-water medium inside us.  We simply could not live without them.

We have now become formally introduced to some of the ways that molecules can communicate among each other.  Redox signaling may be by far the most interesting way of them all.

Welcome to redox signaling country!

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