Schaffer Stephen W, Azuma Junichi, Mozaffari Mahmood
Department of Pharmacology, University of South Alabama, College of Medicine, Mobile, AL 36688, USA.
Can J Physiol Pharmacol. 2009 Feb;87(2):91-9. doi: 10.1139/Y08-110.
The unifying hypothesis of diabetes maintains that reactive oxygen species (ROS) generated in the mitochondria of glucose-treated cells promote reactions leading to the development of diabetic complications. Although the unifying hypothesis attributes the generation of oxidants solely to impaired glucose and fatty acid metabolism, diabetes is also associated with a decline in the levels of the endogenous antioxidant taurine in a number of tissues, raising the possibility that changes in taurine status might also contribute to the severity of oxidant-mediated damage. There is overwhelming evidence that taurine blocks toxicity caused by oxidative stress, but the mechanism underlying the antioxidant activity remains unclear. One established antioxidant action of taurine is the detoxification of hypochlorous acid. However, not all of the antioxidant actions of taurine are related to hypochlorous acid because they are detected in isolated cell systems lacking neutrophils. There are a few studies showing that taurine either modulates the antioxidant defenses or blocks the actions of the oxidants, but other studies oppose this interpretation. Although taurine is incapable of directly scavenging the classic ROS, such as superoxide anion, hydroxyl radical, and hydrogen peroxide, there are numerous studies suggesting that it is an effective inhibitor of ROS generation. The present review introduces a novel antioxidant hypothesis, which takes into consideration the presence of taurine-conjugated tRNAs in the mitochondria. Because tRNA conjugation is required for normal translation of mitochondrial-encoded proteins, taurine deficiency reduces the expression of these respiratory chain components. As a result, flux through the electron transport chain decreases. The dysfunctional respiratory chain accumulates electron donors, which divert electrons from the respiratory chain to oxygen, forming superoxide anion in the process. Restoration of taurine levels increases the levels of conjugated tRNA, restores respiratory chain activity, and increases the synthesis of ATP at the expense of superoxide anion production. The importance of this and other actions of taurine in diabetes is discussed.
糖尿病的统一假说认为，葡萄糖处理细胞的线粒体中产生的活性氧（ROS）会促进导致糖尿病并发症发展的反应。尽管统一假说将氧化剂的产生仅归因于葡萄糖和脂肪酸代谢受损，但糖尿病还与许多组织中内源性抗氧化剂牛磺酸水平的下降有关，这增加了牛磺酸状态变化也可能导致氧化应激介导损伤严重程度的可能性。有大量证据表明牛磺酸可阻止氧化应激引起的毒性，但抗氧化活性的潜在机制仍不清楚。牛磺酸已确定的一种抗氧化作用是对次氯酸的解毒作用。然而，牛磺酸的所有抗氧化作用并非都与次氯酸有关，因为在缺乏中性粒细胞的分离细胞系统中也能检测到这些作用。有一些研究表明牛磺酸可调节抗氧化防御或阻止氧化剂的作用，但其他研究则反对这种解释。尽管牛磺酸无法直接清除经典的ROS，如超氧阴离子、羟基自由基和过氧化氢，但有许多研究表明它是ROS产生的有效抑制剂。本综述介绍了一种新的抗氧化假说，该假说考虑了线粒体中牛磺酸共轭tRNA的存在。由于tRNA共轭是线粒体编码蛋白正常翻译所必需的，牛磺酸缺乏会降低这些呼吸链成分的表达。结果，通过电子传递链的通量减少。功能失调的呼吸链会积累电子供体，这些电子供体将电子从呼吸链转移到氧气，在此过程中形成超氧阴离子。恢复牛磺酸水平可增加共轭tRNA的水平，恢复呼吸链活性，并以超氧阴离子产生为代价增加ATP的合成。文中讨论了牛磺酸的这一作用及其他作用在糖尿病中的重要性。
