Abstract：
:Fumonisins are carcinogenic to rats and are suspected human carcinogens. However, the mechanism(s) of carcinogenesis of fumonisn B1 (FB1) is poorly understood. Multiple signal transduction pathways such as protein kinase C (PKC) have been shown to play an important role in carcinogenesis. This study was undertaken to evaluate whether FB1 affects PKC activation. Similar to tumor-promoting phorbol ester, phorbol 12-myristate-13-acetate (PMA), PKC is also catalytically activated by FB1. Protein kinase C activity and its redistribution in response to FB1 were determined in rat cerebrocortical slices. Cytosolic and membranous PKC activities were determined by histone phosphorylation in the presence of [gamma-32P]ATP, phosphatidyl-L-serine, PMA, and Ca2+. Distribution of gamma PKC isozyme in the presence of FB1 was also assessed by immunoblotting using affinity purified anti-peptide antibodies. Similar to PMA, FB1 added in vitro to rat cerebrocortical slices facilitated PKC translocation from cytosol to membrane in a concentration-dependent manner. This FB1-induced PKC translocation was inhibited by incubation with the inactive 4 alpha-phorbol 12,13-didecanoate. The effects of FB1 and PMA were neither additive nor synergistic. In addition, PMA and FB1-induced PKC enzyme redistribution were inhibited by pretreating tissues with sphingosine. A concentration-related FB1 attenuation of specific phorbol dibutyrate, [3H]PDBu, binding was also observed when cortical membranes were incubated with either PMA or sphingosine. This is the first report of FB1-induced PKC translocation via a direct action on the diacylglycerol site that also binds phorbol esters. Because phorbol esters are well known tumor promoters, we provide a plausible cellular mechanism to explain the carcinogenicity of FB1.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Yeung JM,Wang HY,Prelusky DBdoi
10.1006/taap.1996.0274subject
Has Abstractpub_date
1996-11-01 00:00:00pages
178-84issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(96)90274-4journal_volume
141pub_type
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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