Shao-Hsuan Kao and Tsai-Ching Hsu contributed equally to this work.
Proteomic analysis for the anti-apoptotic effects of cystamine on apoptosis-prone macrophage†
Article first published online: 26 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 110, Issue 3, pages 660–670, 1 June 2010
How to Cite
Kao, S.-H., Hsu, T.-C., Yu, J.-S., Chen, J.-T., Li, S.-L., Lai, W.-X. and Tzang, B.-S. (2010), Proteomic analysis for the anti-apoptotic effects of cystamine on apoptosis-prone macrophage. J. Cell. Biochem., 110: 660–670. doi: 10.1002/jcb.22577
- Issue published online: 20 MAY 2010
- Article first published online: 26 MAR 2010
- Manuscript Accepted: 11 FEB 2010
- Manuscript Received: 13 JUL 2009
- National Science Council Taiwan. Grant Numbers: NSC93-2745-B-040-004-URD, NSC94-2745-B-040-010-URD, NSC97-2314-B-040-008-MY2, DOH98-TD-I-111-TM010
- lupus-prone mice;
- apoptosis-prone macrophages;
Increased macrophage vulnerability is associated with progression of systemic lupus erythematosus. Our previous studies have shown that cystamine, an inhibitor of transglutaminase 2 (TG2), alleviated the apoptosis of hepatocyte and brain cell in lupus-prone mice NZB/W-F1. In present study, we further investigated the effects of cystamine on apoptosis-prone macrophages (APMs) in the lupus mice. Using two-dimensional gel electrophoresis (2-DE) analysis, we found that cystamine induced a differential protein expression pattern of APM as comparing to the PBS control. The protein spots presenting differential level between cystamine and PBS treatment were then identified by peptide-mass fingerprinting (PMF). After bioinformatic analysis, these identified proteins were found involved in mitochondrial apoptotic pathway, oxidative stress, and mitogen-activated protein (MAP) kinase-mediated pathway. Further investigation revealed that cystamine significantly decreased the levels of apoptotic Bax and Apaf-1 and the activity of caspase-3, and increased the levels of anti-apoptotic Bcl-2 in APM. We also found that these apoptotic mediators were up-regulated in a correlation with the progression of lupus severity in NZB/W-F1, which were little affected in BALB/c mice. We also found that the reduced serum glutathione was restored by cystamine in NZB/W-F1. Interestingly, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in APM and the phagocytic ability was diminished in presence of cystamine. In conclusion, our findings indicate that cystamine significantly inhibited mitochondrial pathway, induced antioxidant proteins, and diminished phosphorylation of extracellular ERK1/2, which may alleviate the apoptosis and the phagocytic ability of APM. J. Cell. Biochem. 110: 660–670, 2010. © 2010 Wiley-Liss, Inc.