Signaling Mechanisms of Adaptation to Hypoxia and Its Role in Systemic Regulation

The role of specific hypoxic factor HIF-1 alpha in the urgent and long-term mechanisms of adaptation to hypoxia and its interaction with other signaling pathways, such as free radical processes, cytokines, and NO, have been studied in rats with high and low resistance to hypoxia. It has been shown that this process is genetically determined, occurs only in animals with low resistance to hypoxia and is coupled with biphasic expression of HIF-1 alpha. In animals with high resistance to hypoxia that have no ability to adapt to hypoxic conditions, the expression of HIF-1 alpha is absent or weak. Neither free radical processes, nor cytokines and NO participated in the induction of urgent adaptation and did not interact in this period with changes in the expression of HIF-1 alpha. However, these factors could be important in the formation of long-term adaptation in the animals with low resistance to hypxia. It is assumed that the inducer of urgent adaptation responsible for the formation of the urgent resistance and early posthypoxic HIF-1 alpha accumulation is the succinate-dependent signaling regulatory system controlled by the receptor GPR-91.