Tzang Bor-Show, Chiang Szu-Yi, Lai Wen-Xian, Tsai Chun-Chou, Wu Jen-Huang, Hsu Tsai-Ching
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Int Immunopharmacol. 2008 Apr;8(4):589-96. doi: 10.1016/j.intimp.2008.01.010. Epub 2008 Feb 4.
Increased population with hepatic diseases and apoptosis were found in patients with SLE and implicated in the pathogenesis of SLE. Since cystamine has been demonstrated to be beneficial to NZB/W F1 mice in our previous report, this study intends to investigate the effects of cystamine in liver from NZB/W F1 mice. Decreased apoptosis was detected in liver from NZB/W F1 mice given cystamine as compared to those given PBS by TUNEL and caspase-3 activity assay. Fas-dependent apoptotic proteins including Fas, cleaved caspase-8 and tBid were reduced in liver from NZB/W F1 mice given cystamine as compared to those given PBS. Additionally, the mitochondria-dependent apoptotic proteins including cytochrome c and Apaf-1 were reduced in liver from NZB/W F1 mice given cystamine as compared to those given PBS. Moreover, increased BCL-2 protein was observed in liver from both mice. Notably, increased NF-kappaB protein was detected in liver from NZB/W F1 mice given cystamine as compared to those given PBS. These experimental results suggest the effect of cystamine in reducing apoptosis in liver from NZB/W F1 mice through Fas-dependent and mitochondrial-dependent pathways. The phosphorylation of NF-kappaB (p65) could be a possible mechanism involving anti-apoptotic effects of cystamine in liver from NZB/W F1 mice.
系统性红斑狼疮（SLE）患者中发现肝病和细胞凋亡增加，这与SLE的发病机制有关。由于在我们之前的报告中已证明胱胺对NZB/W F1小鼠有益，本研究旨在探讨胱胺对NZB/W F1小鼠肝脏的影响。通过TUNEL和caspase-3活性检测发现，与给予PBS的小鼠相比，给予胱胺的NZB/W F1小鼠肝脏中的细胞凋亡减少。与给予PBS的小鼠相比，给予胱胺的NZB/W F1小鼠肝脏中Fas依赖性凋亡蛋白包括Fas、裂解的caspase-8和tBid减少。此外，与给予PBS的小鼠相比，给予胱胺的NZB/W F1小鼠肝脏中细胞色素c和Apaf-1等线粒体依赖性凋亡蛋白减少。此外，在两种小鼠的肝脏中均观察到BCL-2蛋白增加。值得注意的是，与给予PBS的小鼠相比，给予胱胺的NZB/W F1小鼠肝脏中检测到NF-κB蛋白增加。这些实验结果表明，胱胺通过Fas依赖性和线粒体依赖性途径减少NZB/W F1小鼠肝脏中的细胞凋亡。NF-κB（p65）的磷酸化可能是胱胺对NZB/W F1小鼠肝脏产生抗凋亡作用的一种可能机制。
