Taurine protects transformed rat retinal ganglion cells from hypoxia-induced apoptosis by preventing mitochondrial dysfunction
Taurine protects transformed rat retinal ganglion cells from hypoxia-induced apoptosis by preventing mitochondrial dysfunction
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DOI：
10.1016/j.brainres.2009.04.054
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发表时间：
2009-07-07
期刊：
影响因子：
2.9
通讯作者：
Zeng, Kaihong
中科院分区：
文献类型：
--
作者：
Chen, Ka;Zhang, Qianyong;Zeng, Kaihong
缺氧诱导的视网膜神经节细胞（RGCs）凋亡是许多视网膜疾病（包括青光眼和糖尿病视网膜病变）中进行性视力丧失的主要原因。牛磺酸是一种天然存在的游离氨基酸，已被证明在视网膜中具有神经营养和神经保护特性。我们研究了牛磺酸对缺氧（5%O-2）永生化大鼠视网膜神经节细胞（RGC-5）的保护作用。用0.1 mM牛磺酸预处理RGC-5细胞显著降低DAPI染色、MTT和Annexin V-FITC/PI检测的凋亡程度。为了进一步研究牛磺酸的有益作用的机制，检测了牛磺酸与RGC-5细胞介导的凋亡过程之间的相互作用。牛磺酸处理RGC-5细胞通过降低细胞内钙水平和抑制线粒体渗透性转换孔（mPTP）的开放来抑制线粒体渗透性转换（mPT）的诱导。此外，在牛磺酸处理的培养物中观察到线粒体膜电位的损失、细胞ATP水平的下降、易位到细胞质的细胞色素c的量的减少和半胱天冬酶-3活化。这些结果表明牛磺酸通过防止线粒体功能障碍来保护RGCs免受体内缺氧损伤的潜力。(C)2009爱思唯尔有限公司版权所有。
Hypoxia-induced apoptosis of retinal ganglion cells (RGCs) is the major cause of progressive vision loss in numerous retinal diseases, including glaucoma and diabetic retinopathy. Taurine is a naturally occurring free amino acid that has been shown to have neurotrophic and neuroprotective properties in the retina. We investigated the specific potential for taurine to be protective for immortalized rat retinal ganglion cells (RGC-5) exposed to hypoxia (5% O-2). Pretreatment of RGC-5 cells with 0.1 mM taurine significantly reduced the extent of apoptosis detected by DAPI staining, MTT, and Annexin V-FITC/PI assays, To further study the mechanism underlying the beneficial effect of taurine, interactions between taurine and the process of mitochondria-mediated apoptosis were examined. Taurine treatment of RGC-5 cells suppressed the induction of the mitochondrial permeability transition (mPT) by reducing intracellular calcium levels and inhibiting the opening of mitochondrial permeability transition pores (mPTPs). Moreover, the loss of mitochondrial membrane potential, a decline in cellular ATP levels, a reduction in the amount of cytochrome c translocated to the cytoplasm and caspase-3 activation were observed in taurine-treated cultures. These results demonstrate the potential for taurine to protect RGCs against hypoxic damage in vivo by preventing mitochondrial dysfunction. (C) 2009 Elsevier B.V. All rights reserved.