Document Detail

Inhibition of benzopyrene-diol-epoxide (BPDE)-induced bax and caspase-9 by cadmium: role of mitogen activated protein kinase.
MedLine Citation:
PMID:  19028507     Owner:  NLM     Status:  MEDLINE    
Cadmium, a major metal constituent of tobacco smoke, elicits synergistic enhancement of cell transformation when combined with benzo[a]pyrene (BP) or other polynuclear aromatic hydrocarbons (PAHs). The mechanism underlying this synergism is not clearly understood. Present study demonstrates that (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), an ultimate carcinogen of BP, induces apoptosis in human leukemic HL-60 cells and others, and cadmium at non-cytotoxic concentration inhibits BPDE-induced apoptosis. We observed that BPDE treatment also activates all three MAP kinases e.g. ERK1/2, p38 and JNK in HL-60 cells, and inhibition of BPDE-induced apoptosis by cadmium is associated with down-regulation of pro-apoptotic bax induction/caspase-9 activation and up-regulation of ERK phosphorylation, whereas p38 MAP kinase and c-Jun phosphorylation (indicative of JNK activation) remain unaffected. Inhibition of ERKs by prior treatment of cells with 10muM U0126 relieves cadmium-mediated inhibition of apoptosis/bax induction/caspase-9 activation. Our results suggest that cadmium inhibits BPDE-induced apoptosis by modulating apoptotic signaling through up-regulation of ERK, which is known to promote cell survival.
Jagat J Mukherjee; Suresh K Gupta; Harish Sikka; Subodh Kumar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-06
Journal Detail:
Title:  Mutation research     Volume:  661     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-02     Completed Date:  2009-04-16     Revised Date:  2010-11-29    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  41-6     Citation Subset:  IM    
State University of New York College at Buffalo, Environ. Toxicol. & Chem., Great Lakes Center, 1300 Elmwood Avenue, Buffalo, NY 14222, United States.
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MeSH Terms
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / toxicity*
Apoptosis / drug effects
Butadienes / pharmacology
Cadmium / toxicity*
Caspase 9 / biosynthesis*
Cell Line
Cell Survival / drug effects
Drug Interactions
Environmental Pollutants / toxicity
Enzyme Induction / drug effects
HL-60 Cells
MAP Kinase Signaling System / drug effects*
Nitriles / pharmacology
Protein Kinase Inhibitors / pharmacology
Signal Transduction / drug effects
Smoke / adverse effects
bcl-2-Associated X Protein / biosynthesis*
Reg. No./Substance:
0/BAX protein, human; 0/Butadienes; 0/Environmental Pollutants; 0/Nitriles; 0/Protein Kinase Inhibitors; 0/Smoke; 0/U 0126; 0/bcl-2-Associated X Protein; 55097-80-8/7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; 7440-43-9/Cadmium; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 9
Erratum In:
Mutat Res. 2010 Oct 13;692(1-2):65
Note: Sikka, Harish [added]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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