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1 January 2004 Role of p38 Mitogen-activated Protein Kinase and Caspases in UV-B–induced Apoptosis of Murine Peritoneal Macrophages
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Abstract

The mechanisms of ultraviolet-B (UV-B)–induced apoptosis and the role of p38 mitogen-activated protein kinase (MAPK) were investigated in murine peritoneal macrophages. Exposure of murine peritoneal macrophages to UV-B irradiation induced rapid apoptosis concurrent with DNA fragmentation and activation of caspase-3 but did not activate caspase-1. UV-B irradiation (100 mJ/cm2) also induced expression of phospho-p38 and –c-Jun N-terminal kinase (JNK) MAPK; however, no significant expression of phospho-p42/44 was observed 120 min after exposure. Pretreatment of macrophages with a p38 MAPK inhibitor, 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole (SB202190), and a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp-CHO, suppressed UV-B irradiation–induced apoptosis as observed by DNA laddering and DNA fragmentation estimation quantitatively. Pretreatment with caspase-1 inhibitor, N-acetyl-Tyr-Val-Ala-Asp-CHO, had no effect. UV-B–induced caspase-3 activation resulted in the cleavage of poly-(ADP-ribose) polymerase (PARP), which was inhibited by the caspase-3 inhibitor. SB202190 pretreatment also prevented activation of caspase-3 and the cleavage of PARP. However, the caspase-3 and -1 inhibitors did not affect UV-B–induced expression of phospho-p38 and -JNK. These results suggest that activation of p38 MAPK upstream of caspases might play an important role in the apoptotic process of macrophages exposed to UV-B irradiation.

Gautam Sethi and Ajit Sodhi "Role of p38 Mitogen-activated Protein Kinase and Caspases in UV-B–induced Apoptosis of Murine Peritoneal Macrophages," Photochemistry and Photobiology 79(1), 48-54, (1 January 2004). https://doi.org/10.1562/0031-8655(2004)79<48:ROPMPK>2.0.CO;2
Received: 14 July 2003; Accepted: 1 October 2003; Published: 1 January 2004
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