Role of cell signalling involved in induction of apoptosis by benzo[a]pyrene and cyclopenta[c,d]pyrene in Hepa1c1c7 cells

✍ Scribed by Anita Solhaug; Magne Refsnes; Jørn A. Holme

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 391 KB
• Volume: 93
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20251

✦ Synopsis

Abstract

The reactive metabolites of benzo[a]pyrene (B[a]P) and cyclopenta[c,d]pyrene (CPP) induced an accumulation/phosphorylation of p53 in Hepa1c1c7 cells, whereas inhibition of p53 reduced the apoptosis. Judged by the inhibiting effect of wortmannin, phosphatidyl‐inositol‐3 (PI‐3) kinases such as DNA‐dependent protein kinase (DNA‐PK), ATM (ataxia‐telangiectasia mutated), and/or ATR (ATM related kinase), appeared to be involved in the DNA damage recognition and the B[a]P‐/CPP‐induced accumulation of p53. B[a]P and CPP also induced phosphorylation of jun‐N‐terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). While inhibition of JNK had no effects on the B[a]P‐/CPP‐induced apoptosis, inhibition of p38 MAPK activity reduced this effect. Interestingly, survival signals such as phosphorylation of Akt and Bad seemed to be induced by the B[a]P‐/CPP‐compounds. Furthermore, also extracellular signal‐regulated kinase (ERK)1/2 was activated and seemed to function as a survival signal in B[a]P‐/CPP‐induced apoptosis. © 2004 Wiley‐Liss, Inc.