Treatment with cystamine reduces apoptosis in liver from NZB/W F1 mice.
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.
Tzang
Bor-Show
BS
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, ROC. bstzang@csmu.edu.tw
Chiang
Szu-Yi
SY
Lai
Wen-Xian
WX
Tsai
Chun-Chou
CC
Wu
Jen-Huang
JH
Hsu
Tsai-Ching
TC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D003538:Cystamine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000473:pathology*; D051379:Mice; D008814:Mice, Inbred NZB; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D051023:BH3 Interacting Domain Death Agonist Protein; D053148:Caspase 3; D053181:Caspase 8; D003538:Cystamine; D004791:Enzyme Inhibitors; D017346:Protein Serine-Threonine Kinases; D051996:Transcription Factor RelA; D051025:bcl-Associated Death Protein; D019014:fas Receptor; D000097782:NF-kappaB-Inducing Kinase; C498144:Rela protein, mouse; C505526:Casp8 protein, mouse