Thyroid hormones and regulation of cell reliability systems.
Data and arguments are presented that provide evidence of a role played by thyroid hormones (TH) in cell reliability improvement. This role may be determined by synergistic TH action on the following key cell reliability systems: (1) reactive oxygen species (ROS) attack inhibition, and (2) genetic structure repair from injuries inflicted in the course of endogenous and induced mutagenesis. (1) New approaches to ROS oxidation defence were examined. It has been shown that Ca(2+)-ATPase and, probably, regulatory proteins of cell membranes may be the main target for oxidative attack. Protein phosphorylation as well as use of dithiothreitol will lead to a protective action against Ca2+ transport damaging in aorta smooth muscle sarcoplasmic reticulum under oxidation by HOCl, the most toxic ROS of activated neutrophils, whereas thyroxine (T4) and 3,5,3'-triiodothyronine (T3) validly inhibit chemiluminescence in human neutrophils activated by pyrogenal, a lipopolysaccharide from Salmonella typhi cell wall. As this takes place, TH most likely block neutrophil stimulation at the receptor-ligand interaction level. In this case L-T4 and L-T3 antioxidative effect is greater than that of DL-thyroxine and much greater than that produced by such a potent antioxidant as 4-methyl-2,6-diisobutyl phenol. (2) T4 acts as reparogen in rat liver cells under X-ray irradiation when a dose measuring one-half of daily hormone production by the normally functioning thyroid gland is administered to animals. Ionizing radiation dose reduction factor reached 1.3-1.4 following T4 administration. Reparogenic effect of T4 persists for at least 2 months from the moment the hormone has been administered and can be reduced in the presence of dinitrophenol. It is important to note that antioxidant and reparogenic TH potential can manifest itself within the range of physiologic concentrations of these hormones. Therefore, stimulation of cell reliability systems with TH may prove to be important for correcting conditions caused by errors in energy- and Ca(2+)-dependent DNA repair under extensive ROS attack. In particular, taking into account different responsiveness of normal and neoplastic tissues to TH, the use of TH reparogenic as well as antioxidant potential may contribute significantly to the improvement of antitumor radiotherapy efficacy.
Antipenko AYe
Institute of Physiology, St. Petersburg University, Russia.
Antipenko
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004734:Energy Metabolism / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009369:Neoplasms / Q000209:etiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010766:Phosphorylation; D011817:Rabbits; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D013963:Thyroid Hormones / Q000494:pharmacology*; D014965:X-Rays / Q000009:adverse effects
D000975:Antioxidants; D013963:Thyroid Hormones; D000252:Calcium-Transporting ATPases; D002118:Calcium