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Role of p38 Mitogen‐activated Protein Kinase and Caspases in UV‐B‐induced Apoptosis of Murine Peritoneal Macrophages ¶
Author(s) -
Sethi Gautam,
Sodhi Ajit
Publication year - 2004
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2004.tb09856.x
Subject(s) - p38 mitogen activated protein kinases , apoptosis , dna fragmentation , dna laddering , poly adp ribose polymerase , microbiology and biotechnology , protein kinase a , caspase , mapk/erk pathway , kinase , chemistry , caspase 3 , biology , biochemistry , programmed cell death , polymerase , enzyme
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/cm 2 ) 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)‐1 H ‐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.