Pharmacobiochemical Laboratory of 3rd Medical Department, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Center of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Can J Physiol Pharmacol. 2020 Jan;98(1):29-34. doi: 10.1139/cjpp-2019-0281. Epub 2019 Sep 19.
Mitochondria are the major source of cellular energy metabolism. In the cardiac cells, mitochondria produce by way of the oxidative phosphorylation more than 90% of the energy supply in the form of ATP, which is utilized in many ATP-dependent processes, like cycling of the contractile proteins or maintaining ion gradients. Reactive oxygen species (ROS) are by-products of cellular metabolism and their levels are controlled by intracellular antioxidant systems. Imbalance between ROS and the antioxidant defense leads to oxidative stress and oxidative changes to cellular biomolecules. Molecular hydrogen (H) has been proved as beneficial in the prevention and therapy of various diseases including cardiovascular disorders. It selectively scavenges hydroxyl radical and peroxynitrite, reduces oxidative stress, and has anti-inflammatory and anti-apoptotic effects. The effect of H on the myocardial mitochondrial function and coenzyme Q levels is not well known. In this paper, we demonstrated that consumption of H-rich water (HRW) resulted in stimulated rat cardiac mitochondrial electron respiratory chain function and increased levels of ATP production by Complex I and Complex II substrates. Similarly, coenzyme Q levels in the rat plasma, myocardial tissue, and mitochondria were increased and malondialdehyde level in plasma was reduced after HRW administration. Based on obtained data, we hypothesize a new metabolic pathway of the H effect in mitochondria on the Q-cycle and in mitochondrial respiratory chain function. The Q-cycle contains three coenzyme Q forms: coenzyme Q in oxidized form (ubiquinone), radical form (semiquinone), or reduced form (ubiquinol). H may be a donor of both electron and proton in the Q-cycle and thus we can suppose stimulation of coenzyme Q production. When ubiquinone is reduced to ubiquinol, lipid peroxidation is reduced. Increased CoQ concentration can stimulate electron transport from Complex I and Complex II to Complex III and increase ATP production via mitochondrial oxidative phosphorylation. Our results indicate that H may function to prevent/treat disease states with disrupted myocardial mitochondrial function.
线粒体是细胞能量代谢的主要来源。在心脏细胞中，线粒体通过氧化磷酸化产生超过 90%的以 ATP 形式存在的能量供应，ATP 用于许多依赖于 ATP 的过程，如收缩蛋白的循环或离子梯度的维持。活性氧（ROS）是细胞代谢的副产物，其水平由细胞内抗氧化系统控制。ROS 和抗氧化防御之间的失衡导致氧化应激和细胞生物分子的氧化变化。分子氢（H）已被证明对预防和治疗各种疾病（包括心血管疾病）有益。它选择性地清除羟自由基和过氧亚硝酸盐，降低氧化应激，并具有抗炎和抗凋亡作用。H 对心肌线粒体功能和辅酶 Q 水平的影响尚不清楚。在本文中，我们证明了富氢水（HRW）的消耗导致大鼠心肌线粒体电子呼吸链功能增强，并且通过 I 复合物和 II 复合物底物增加了 ATP 的产生。同样，HRW 给药后，大鼠血浆、心肌组织和线粒体中的辅酶 Q 水平增加，血浆中的丙二醛水平降低。基于获得的数据，我们假设 H 在 Q 循环和线粒体呼吸链功能中对线粒体的作用的新代谢途径。Q 循环包含三种辅酶 Q 形式：氧化形式（泛醌）、自由基形式（半醌）或还原形式（泛醇）。H 可能是 Q 循环中电子和质子的供体，因此我们可以假设辅酶 Q 的产生受到刺激。当泛醌还原为泛醇时，脂质过氧化作用减少。增加的 CoQ 浓度可以刺激从 I 复合物和 II 复合物到 III 复合物的电子传递，并通过线粒体氧化磷酸化增加 ATP 的产生。我们的结果表明，H 可能具有预防/治疗心肌线粒体功能障碍疾病状态的功能。
