The Role of Mitochondrial Enzymes, Succinate-Coupled Signaling Pathways and Mitochondrial Ultrastructure in the Formation of Urgent Adaptation to Acute Hypoxia in the Myocardium.

The effect of a single one-hour exposure to three modes of hypobaric hypoxia (HBH) differed in the content of O in inhaled air (FiO-14%, 10%, 8%) in the development of mitochondrial-dependent adaptive processes in the myocardium was studied in vivo. The following parameters have been examined: (a) an urgent reaction of catalytic subunits of mitochondrial enzymes (NDUFV2, SDHA, Cyt b, COX2, ATP5A) in the myocardium as an indicator of the state of the respiratory chain electron transport function; (b) an urgent activation of signaling pathways dependent on GPR91, HIF-1α and VEGF, allowing us to assess their role in the formation of urgent mechanisms of adaptation to hypoxia in the myocardium; (c) changes in the ultrastructure of three subpopulations of myocardial mitochondria under these conditions. The studies were conducted on two rat phenotypes: rats with low resistance (LR) and high resistance (HR) to hypoxia.

Signaling Role of Mitochondrial Enzymes and Ultrastructure in the Formation of Molecular Mechanisms of Adaptation to Hypoxia.

This study was the first comprehensive investigation of the dependence of mitochondrial enzyme response (catalytic subunits of mitochondrial complexes (MC) I-V, including NDUFV2, SDHA, Cyt b, COX1 and ATP5A) and mitochondrial ultrastructure in the rat cerebral cortex (CC) on the severity and duration of in vivo hypoxic exposures. The role of individual animal's resistance to hypoxia was also studied. The respiratory chain (RC) was shown to respond to changes in environmental [O] as follows: (a) differential reaction of mitochondrial enzymes, which depends on the severity of the hypoxic exposure and which indicates changes in the content and catalytic properties of mitochondrial enzymes, both during acute and multiple exposures; and (b) ultrastructural changes in mitochondria, which reflect various degrees of mitochondrial energization.

[The effect of Mexidol on cerebral mitochondriogenesis at a young age and during aging].

Aim: To study the ability of mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats.

Material And Methods: Expression level of marker proteins of cerebral mitochondriogenesis was evaluated during treatment with mexidol (20, 40, 100 mg/kg; 20 days; intraperitoneally) in the cerebral cortex of young (3 month) and aging (6, 9, 12, and 15 month) outbred male rats, using the Western blot analysis.

Results: It has been shown for the first time that the course injections of mexidol in doses of 40 and 100 mg/kg is accompanied by dose-dependent induction of the succinate receptor SUCNR1 and protein markers of mitochondrial biogenesis: transcription coactivator PGC-1α, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUV2, NDUV2,cytb, COX2) and ATP synthase (ATP5A) in the cerebral cortex of young and aging outbred male rats.

Effect of hypoxia on mitochondrial enzymes and ultrastructure in the brain cortex of rats with different tolerance to oxygen shortage.

The mitochondrial structure and the contents of subunits (NDUFV2, SDHA, Cyt b, COX1) of mitochondrial respiratory complexes I-IV as well as of the hypoxia-inducible factor (HIF-1α) in the brain cortex (BC) of rats with high resistance (HR) and low resistance (LR) to hypoxia were studied for the first time depending on the severity of hypoxia. Different regimes of 30-min hypobaric hypoxia (pO 14, 10, and 8%) were used. It was found that cortical mitochondria responded to 30-min hypobaric hypoxia of different severity with typical and progressing changes in mitochondrial structure and function of mitochondrial enzymes.

Peculiarities of Immediate Response of Respiratory Chain Enzymes in Rat Cerebral Cortex to Hypoxia.

We performed a complex study of the dependence of immediate reaction of catalytic subunits in mitochondrial enzymes (NDUFV2, SDHA, Cyt b, COX1, and ATP5A) in rat cerebral cortex (the most hypoxia-sensitive tissue) on the severity and duration of hypoxia in vivo and the role of individual resistance of rats to oxygen deficiency in this process. Three types of responses to hypoxia were revealed. The immediate response of mitochondria to oxygen deficiency appeared after its drop by 30-33% relatively to normal atmosphere level.