Caspase-9 and Bax/Bcl-2 Regulation in Ultraviolet B-Induced Apoptosis of Murine Peritoneal Macrophages

Abstract

This study was performed to determine the effect of UVB radiation on the activation of apoptosis regulatory proteins using murine peritoneal macrophages, which are terminally, differentiated nondividing cells. UVB (100 mJ/cm2) irradiation induced apoptosis in murine peritoneal macrophages concurrent with expression of p53, Apaf-1, upregulation of Bax, downregulation of Bcl-2, activation of caspases-9, -3, -2 and DNA fragmentation. Pretreatment of macrophages with serine protease inhibitors TPCK and TLCK inhibitedUVBirradiation induced apoptosis. Interestingly, caspase-9 inhibitor Z-LEHD-FMK blocked caspase-2 activation suggesting that caspase-2 activation is not due to death receptor activation but results from activation of other caspases that are dependent on caspase-9 such as caspase-3. The data showed that the regulation of the Bcl-2 family and caspase-9 might work together to activate a caspase-3 mediated apoptotic pathway following UVB irradiation of macrophages.

Keywords :

• Bax/Bcl-2
• Caspase-9
• Macrophages
• Serine Proteases
• Ultraviolet-B

This work has been supported by grants from Department of Biotechnology, Government of India, and University Grants Commission, New Delhi to Prof. A. Sodhi. Gautam Sethi is a recipient of CSIR-SRF.