Studying
Cellular Stress
With Molecular Chaperones
E-Newsletter No. 39
The classic method used to induce a stress response in cells is to expose them to excess heat (but not too much, just a couple of degrees does the trick), a process called "heat shock." Shocking cells with heat (or other stressors, such as cold, salt, toxins, or a variety of hormones causes the cells to increase their production of a specific set of proteins, inventively called heat-shock proteins. These proteins help the cell survive stress.
Some of these antistress heat-shock proteins are called chaperonins, a term that hints at their functions as "molecular chaperones." In this role, they help other proteins in the cell to maintain their normal structure (which is typically characterized by very complex, intricate folding of the long chains of amino acids that are the building blocks that made up the structures of all proteins). Heat and other stressors can cause proteins to denature, which means they lose their normal shape through an unfolding of this complex chain of amino acids. Whenever this happens, a protein will lose its normal function, because its form is critical to its function. This denatured protein is then further degraded and ultimately destroyed within the cell by specific chemical reactions known as an enzymatic degradation.
Chaperonins help the cell survive this stress by helping the denatured proteins to fold back into their normal shape. They will even help to refold misshapen proteins. Thus, they can restore the function of these proteins, many of which are critical enzymes with vital tasks to perform. Chaperonins are essential to cell survival under stressful conditions in order to allow them to maintain normal metabolism, growth, and maturation.
Of the 2,000 intracellular proteins that are known, only a few are thought to be heat-shock proteins (Hsp). Heat-shock protein
70 (Hsp 70) is thought to be the most important in helping cellular proteins to regain their normal structure so they can remain functional.
In addition to Hsp 70, there are other antistress proteins that perform vital functions. There are two cytochrome P-450 enzymes (EROD and PROD), both of which are important detoxification enzymes. They protect the body from certain toxins by converting them to less harmful compounds. The enzyme superoxide dismutase (SOD), an antioxidant, dismantles especially destructive free-radicals called superoxides, converting them to harmless organic compounds, water, and hydrogen peroxide (H2O2). This latter, H2O2 is then further inactivated by another antioxidant enzyme, glutathione peroxidase, to oxygen and water.
Studies of cellular stress indicated that the cells can become programmed to resist stress by adapting to
it, caloric restriction, or exposure to increased temperature (the equivalent to sitting in a sauna for 15 minutes a day) to raise Hsp
70 levels, or ingesting a small amount of BHT (Butylated hydroxytoluene), an oil-soluble synthetic antioxidant food preservative, to induce increased activity of the cytochrome P-450 oxidase enzyme system, as well as other antioxidants such as vitamin E, alpha-lipoic acid or vitamins B1 and C in combination with N-acetyl cysteine which are well documented to raise glutathione levels, can have beneficial effects. When used in this fashion, these are all called "adaptogens", because they help program the cell to adapt to stress for survival. Who knows, they also might have some antiaging benefits, too.
Footnotes:
EROD is the abbreviation for the chemical structure
7-ethoxyresorufin-o-deethylase.
PROD is described as 7-pentoxyresorufin-o-dealkylase
