Role of Mitochondria and Endoplasmic Reticulum in Taurine-Deficiency-Mediated Apoptosis.
Role of Mitochondria and Endoplasmic Reticulum in Taurine-Deficiency-Mediated Apoptosis.
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DOI：
10.3390/nu9080795
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发表时间：
2017-07-25
期刊：
影响因子：
5.9
通讯作者：
Schaffer SW
中科院分区：
文献类型：
--
作者：
Jong CJ;Ito T;Prentice H;Wu JY;Schaffer SW
牛磺酸是一种普遍存在的含硫氨基酸，在大多数组织中含量很高。牛磺酸参与调节呼吸链活性、调节阳离子转运、控制炎症、改变蛋白质磷酸化和延长寿命等基本生理功能，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还不够清楚。因此，本研究验证了呼吸链复合体I过量产生活性氧物种(ROS)触发牛磺酸转运蛋白基因敲除(TauTKO)小鼠心脏线粒体依赖性细胞凋亡的假说。为了支持这一假设，观察到3个月龄的TauTKO心脏线粒体牛磺酸含量下降了60%，这与复合体I活性降低和线粒体氧化应激的开始有关。应激对线粒体的氧化损伤导致caspase级联激活，而caspase 9和caspase 3的刺激可以通过用线粒体特有的抗氧化剂MitoTEMPO治疗3个月大的TauTKO小鼠来阻止。在12个月大而不是3个月大的TauTKO心脏中，caspase 12的激活有助于细胞死亡，揭示了牛磺酸缺乏的衰老小鼠内质网(ER)应激的病理作用。因此，牛磺酸是一种细胞保护性营养物质，可以确保正常的线粒体和内质网功能，这对降低细胞凋亡和过早死亡的风险非常重要。
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.
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影响因子：
20.1
作者：
Chen Y;Csordás G;Jowdy C;Schneider TG;Csordás N;Wang W;Liu Y;Kohlhaas M;Meiser M;Bergem S;Nerbonne JM;Dorn GW 2nd;Maack C
通讯作者：
Maack C
影响因子：
7.2
作者：
Martinez, Juan A.;Zhang, Zhiqun;Larner, Stephen F.
通讯作者：
Larner, Stephen F.
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
DOI：
10.1111/j.1582-4934.2006.tb00407.x
发表时间：
2006-04
影响因子：
5.3
作者：
Dalle-Donne I;Aldini G;Carini M;Colombo R;Rossi R;Milzani A
通讯作者：
Milzani A
影响因子：
4.8
作者：
Chen, Q;Vazquez, EJ;Lesnefsky, EJ
通讯作者：
Lesnefsky, EJ