Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
Faculty of Biotechnology, Fukui Prefectural University, Fukui 910-1195, Japan.
Nutrients. 2017 Jul 25;9(8):795. doi: 10.3390/nu9080795.
Taurine is a ubiquitous sulfur-containing amino acid found in high concentration in most tissues. Because of its involvement in fundamental physiological functions, such as regulating respiratory chain activity, modulating cation transport, controlling inflammation, altering protein phosphorylation and prolonging lifespan, taurine is an important nutrient whose deficiency leads to severe pathology and cell death. However, the mechanism by which taurine deficiency causes cell death is inadequately understood. Therefore, the present study examined the hypothesis that overproduction of reactive oxygen species (ROS) by complex I of the respiratory chain triggers mitochondria-dependent apoptosis in hearts of taurine transporter knockout (TauTKO) mice. In support of the hypothesis, a 60% decrease in mitochondrial taurine content of 3-month-old TauTKO hearts was observed, which was associated with diminished complex I activity and the onset of mitochondrial oxidative stress. Oxidative damage to stressed mitochondria led to activation of a caspase cascade, with stimulation of caspases 9 and 3 prevented by treatment of 3-month-old TauTKO mice with the mitochondria specific antioxidant, MitoTempo. In 12 month-old, but not 3-month-old, TauTKO hearts, caspase 12 activation contributes to cell death, revealing a pathological role for endoplasmic reticulum (ER) stress in taurine deficient, aging mice. Thus, taurine is a cytoprotective nutrient that ensures normal mitochondrial and ER function, which is important for the reduction of risk for apoptosis and premature death.
牛磺酸是一种广泛存在的含硫氨基酸,在大多数组织中都以高浓度存在。由于其参与基本的生理功能,如调节呼吸链活性、调节阳离子转运、控制炎症、改变蛋白质磷酸化和延长寿命,牛磺酸是一种重要的营养物质,其缺乏会导致严重的病理和细胞死亡。然而,牛磺酸缺乏导致细胞死亡的机制尚未充分了解。因此,本研究检验了以下假设:即呼吸链复合体 I 产生的活性氧(ROS)过多会引发牛磺酸转运体敲除(TauTKO)小鼠心脏中的线粒体依赖性细胞凋亡。该假设得到了支持,研究观察到 3 个月大的 TauTKO 心脏中线粒体牛磺酸含量减少了 60%,这与复合体 I 活性降低和线粒体氧化应激的发生有关。受应激的线粒体发生氧化损伤,导致半胱氨酸蛋白酶级联激活,用线粒体特异性抗氧化剂 MitoTempo 处理 3 个月大的 TauTKO 小鼠可阻止半胱氨酸蛋白酶 9 和 3 的激活。在 12 个月大的 TauTKO 心脏中,但在 3 个月大的 TauTKO 心脏中没有观察到,半胱天冬酶 12 的激活导致细胞死亡,这揭示了内质网(ER)应激在牛磺酸缺乏、衰老小鼠中的病理作用。因此,牛磺酸是一种细胞保护营养物质,可确保正常的线粒体和 ER 功能,这对于降低细胞凋亡和过早死亡的风险很重要。