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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