Do the Effects of Krebs Cycle Intermediates on Oxygen-Dependent Processes in Hypoxia Mediated by the Nitric Oxide System Have Reciprocal or Competitive Relationships?

IF 2.5 Q3 CELL BIOLOGY Cellular Physiology and Biochemistry Pub Date : 2023-11-15 DOI:10.33594/000000669
Natalia Kurhaluk, Oleksandr Lukash, Halina Tkaczenko
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Abstract

Background/aims: Currently, it is proven that the cellular metabolism of nitric oxide is necessary to maintain optimal health and adaptation of the organism to the impact of various environmental factors. The aim of this work was to reveal the biological role of nitric oxide, its metabolic changes, and its mechanism of action in tissues under hypoxia, as well as the possibility of tissue metabolism correction through NO-dependent systems under the influence of Krebs cycle intermediates.

Methods: A systematic assessment of the effect of succinate (SC, 50 mg/kg b.w.) and α-ketoglutarate (KGL, 50 mg/kg b.w.) in the regulation of oxygendependent processes in rats (mitochondrial oxidative phosphorylation, microsomal oxidation, intensity of lipid peroxidation processes, and the state of the antioxidant defense system) depending on functional changes in nitric oxide production during hypoxia was evaluated. The state of the nitric oxide system was estimated spectrophotometrically by determination of the concentration of its stable nitrite anion metabolite (NO2 -). The levels of catecholamines were estimated from the content of epinephrine and norepinephrine using the differentially fluorescent method. The activity of cytochrome P450-dependent aminopyrine-N-demethylase was determined with the Nash reagent.

Results: Tissue hypoxia and metabolic disorders caused by this condition through changes in the content of catecholamines (epinephrine, norepinephrine, dopamine, DOPA) as well as the cholinesterase-related system (acetylcholine content and acetylcholinesterase activity) were the studied experimental parameters under acute hypoxia (AH, 7% O2 in N2, 30 min). The activation of lipid peroxidation and oxidatively modified proteins and an increase in the epinephrine content in AH are associated with an increased role of SC and a decrease in KGL as substrates of oxidation in mitochondria. A more pronounced effect of exogenous KGL, compared to SC, on the content of nitrite anion as a stable metabolite of nitric oxide in the liver under acute hypoxia against the background of a decrease in the intensity of lipid peroxidation processes was revealed. The activation of SC-dependent mitochondrial oxidative processes caused by AH was found to decrease in animals after an intermittent hypoxia training (IHT) course. IHT (7% O2 in N2, 15-min, 5 times daily, 14 days) prevented the activation of oxidative stress in tissues and blood after the AH impact and increased the efficiency of energy-related reactions in the functioning of hepatic mitochondria through increased oxidation of KGL.

Conclusion: The studied effects of adaptation are mediated by an increase in the role of NO-dependent mechanisms, as assessed by changes in the pool of nitrates, nitrites, carbamides, and total polyamines.

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由一氧化氮系统介导的缺氧中克雷布斯循环中间体对氧依赖过程的影响是否具有互惠或竞争关系?
背景/目的:目前已经证明,一氧化氮的细胞代谢是维持机体最佳健康和适应各种环境因素影响所必需的。本研究旨在揭示缺氧条件下一氧化氮的生物学作用、代谢变化及其在组织中的作用机制,以及在克雷布斯循环中间体的影响下,一氧化氮依赖系统对组织代谢进行校正的可能性。方法:系统评估琥珀酸盐(SC, 50 mg/kg b.w.)和α-酮戊二酸盐(KGL, 50 mg/kg b.w.)对缺氧时一氧化氮生成的功能变化对大鼠氧依赖过程(线粒体氧化磷酸化、微粒体氧化、脂质过氧化过程强度和抗氧化防御系统状态)的调节作用。用分光光度法测定其稳定的亚硝酸盐阴离子代谢物(NO2 -)的浓度来估计一氧化氮体系的状态。儿茶酚胺的水平是用差异荧光法从肾上腺素和去甲肾上腺素的含量来估计的。采用Nash试剂测定细胞色素p450依赖性氨基吡啶- n -去甲基化酶的活性。结果:研究急性缺氧(AH, 7% O2 in N2, 30min)下组织缺氧及由此引起的儿茶酚胺(肾上腺素、去甲肾上腺素、多巴胺、多巴胺)含量变化及胆碱酯酶相关系统(乙酰胆碱含量和乙酰胆碱酯酶活性)代谢紊乱的实验参数。AH中脂质过氧化和氧化修饰蛋白的激活以及肾上腺素含量的增加与SC作为线粒体氧化底物的作用增加和KGL的减少有关。与SC相比,外源性KGL对急性缺氧下肝脏中一氧化氮的稳定代谢物亚硝酸盐阴离子含量的影响更为明显,其背景是脂质过氧化过程的强度降低。间歇性缺氧训练(IHT)后,发现AH引起的sc依赖性线粒体氧化过程的激活减少。IHT (7% O2在N2中,15分钟,每天5次,14天)阻止AH冲击后组织和血液中氧化应激的激活,并通过增加KGL的氧化提高肝线粒体功能中能量相关反应的效率。结论:通过硝酸盐、亚硝酸盐、氨酰胺和总多胺的变化来评估,所研究的适应效应是由no依赖机制的作用增加介导的。
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来源期刊
CiteScore
5.80
自引率
0.00%
发文量
86
审稿时长
1 months
期刊介绍: Cellular Physiology and Biochemistry is a multidisciplinary scientific forum dedicated to advancing the frontiers of basic cellular research. It addresses scientists from both the physiological and biochemical disciplines as well as related fields such as genetics, molecular biology, pathophysiology, pathobiochemistry and cellular toxicology & pharmacology. Original papers and reviews on the mechanisms of intracellular transmission, cellular metabolism, cell growth, differentiation and death, ion channels and carriers, and the maintenance, regulation and disturbances of cell volume are presented. Appearing monthly under peer review, Cellular Physiology and Biochemistry takes an active role in the concerted international effort to unravel the mechanisms of cellular function.
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