Cystamine attenuates lupus-associated apoptosis of ventricular tissue by suppressing both intrinsic and extrinsic pathways.
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.
Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung City, Taiwan.
Bor-Show
BS
Tzang
Tsai-Ching
TC
Hsu
Cheng-Yi
CY
Kuo
Tzy-Yen
TY
Chen
Szu-Yi
SY
Chiang
Sin-Lun
SL
Li
Shao-Hsuan
SH
Kao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003538:Cystamine / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling / Q000379:methods; D008180:Lupus Erythematosus, Systemic / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D051023:BH3 Interacting Domain Death Agonist Protein; C494820:Bad protein, mouse; C491899:Fas protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D019014:fas Receptor; C052617:Bcl2 protein, mouse; D045304:Cytochromes c; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D003538:Cystamine