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

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.

• Authors: Anita Solhaug, Magne Refsnes, Jørn A Holme
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 93 Issue 6 Pg. 1143-54 (Dec 15 2004) ISSN: 0730-2312 [Print] United States
• PMID: 15449320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 Wiley-Liss, Inc.

Chemical References

• DNA-Binding Proteins
• Pyrenes
• Tumor Suppressor Protein p53
• cyclopenta(c,d)pyrene
• Benzo(a)pyrene
• Mitogen-Activated Protein Kinase 9
• DNA-Activated Protein Kinase
• Protein Serine-Threonine Kinases
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Benzo(a)pyrene (toxicity)
• Cell Membrane (drug effects)
• DNA-Activated Protein Kinase
• DNA-Binding Proteins (metabolism)
• Enzyme Activation (drug effects)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Mice
• Mitogen-Activated Protein Kinase 9 (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Pyrenes (toxicity)
• Signal Transduction (drug effects, physiology)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)