Cystamine attenuates lupus‐associated apoptosis of ventricular tissue by suppressing both intrinsic and extrinsic pathways

Journal of Cellular and Molecular Medicine

Bor-Show Tzang⁵  Tsai-Ching Hsu³  Cheng-Yi Kuo¹  Tzy-Yen Chen⁶  Szu-Yi Chiang⁴  Sin-Lun Li² 

[1] Seeing BioScience Co Ltd., New Taipei City, Taiwan;Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung City, Taiwan;Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City, Taiwan;Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan;Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung City, Taiwan;Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

关键词: apoptosis;    cystamine;    Fas;    lupus‐prone mice;    ventricular tissue;   

DOI  :  10.1111/j.1582-4934.2011.01511.x

来源: Wiley

【 摘 要 】

Abstract

Cystamine, a disulphide metabolite, has been demonstrated to ameliorate various lupus-associated tissue damages by animal models. However, effects of cystamine on apoptosis of cardiac tissue, a main cardiac damage attributing to lupus, are less obvious. Therefore, we aimed to investigate whether or not cystamine possesses anti-apoptotic effects with emphasis on LV tissue of lupus-prone mice NZB/W-F1. Cystamine treatment was performed by daily intraperitoneal administration. Morphology and apoptotic status of ventricular tissues in the treated mice were assessed by microscopy and TUNEL assay, respectively. Levels of apoptotic biomarkers were determined using immunoblot. Our results revealed that cystamine significantly attenuated the apoptosis of LV tissues in NZB/W-F1 mice, whereas the morphology of the tissues was slightly altered. In addition, cystamine reduced level of Fas and inhibited activation of caspase-8. Cystamine also increased level of Bcl-2 and phosphorylation of Bad, and decreased level of Bad and truncated Bid (tBid). Moreover, level of cytosolic cytochrome c and Apaf-1, and activation of caspase-9 and caspase-3 were suppressed in response to cystamine treatment. In Balb/c mice, as normal control mice, changes in cell morphology and levels of the tested apoptotic components were found insignificant in the LV tissues. These findings indicate that cystamine treatment attenuates apoptosis of LV tissues of NZB/W-F1 mice through suppressing both intrinsic and extrinsic apoptotic pathways. Therefore, cystamine is considered beneficial to alleviating lupus-associated cardiac damages.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd