[Molecular mechanisms of tissue hypoxia and organism adaptation].
The mechanism for participation of aerobic energy metabolism in formation of urgent and long-term adaptation to hypoxia is under consideration. It is stated that changes in kinetic properties of mitochondrial enzyme complexes (MEC), primarily enzymes of the respiratory chain substrate region (MEC I), in response to oxygen shortage underlie diverse stages of bioenergetic (tissue) hypoxia. It was shown that economization of energy metabolism in adaptation to hypoxia occurs due to formation of a new mitochondrial population. The mitochondria possess lesser size and decreased content of cytochromes; however, they are characterized by higher activities of enzymes and lower affinity of the enzymes to their substrates as well as high efficiency of oxidative phosphorylation. Furthermore the amount of mitochondria increases in the cell. It was demonstrated that oxygen shortage can both directly affect the bioenergetic apparatus of cell and indirectly influence it via stress activation of the neuro-humoral system. The latter triggers a non-specific cascade of functional and metabolic responses and eventually disturbs oxygen delivery to cells, which also promotes bioenergetic hypoxia. Genotypically determined differences in kinetic properties of MEC are established, which play a leading role in formation of the functional and metabolic "portrait" of resistant and non-resistant to hypoxia animals and also in development of urgent and long-term mechanisms of adaptation to hypoxia. It was shown that these mechanisms can be used not only for development of the tactics and strategy for pharmacological correction of hypoxic states, but also for optimization of non-drug methods for enhancing the non-specific resistance of the organism.
Luk'ianova
L D
LD
Research Institute for General Pathology and Pathophysiology, RAS, Moskow.
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism
D010100:Oxygen