Source:http://linkedlifedata.com/resource/pubmed/id/10382866
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1999-7-27
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pubmed:abstractText |
Aflatoxin B1 (AFB1) action on cyclic nucleotide phosphodiesterase (PDE) activity has been tested on tissue extracts of various organs. In the presence of 100 microM AFB1 a significant inhibition of cAMP and cGMP hydrolytic activity is observed in all tested tissue extracts. However, cGMP hydrolytic activity appears more sensitive to AFB1 inhibition than cAMP hydrolytic activity and a considerably higher inhibition is observed in lung and spleen, than in liver, brain, kidney, and heart. When cGMP is used as substrate, the inhibitory response reaches 72% in lung and spleen extracts. We have also tested AFB1 effects on lung and liver PDE activity peaks separated by DEAE-cellulose chromatography. These data confirm the poor sensitivity to the toxin of all PDE activities present in liver, while the lung peak (where PDE V in present) shows a higher sensitivity to AFB1. In order to establish whether PDE V is in fact more sensitive to AFB1, we have used mouse neuroblastoma cells, in which cGMP hydrolytic activity has been shown to be due to PDE V only. In this case, the calculated IC50 is 24 microM and Dixon plot analysis shows a competitive inhibitory effect with a Ki of 16.7 microM. We have also used aflatoxin B2 and M2, and they proved to be much less effective than AFB1: AFB2 inhibits PDE V with an IC50 of 117 microM, while AFM2 does not show any effect. These results provide the first evidence of a competitive inhibition of AFB1 on an enzymatic activity and suggest that an alteration of cellular cyclic nucleotide levels may play a role in the mechanism of aflatoxin action.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0306-3623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
615-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10382866-3',5'-Cyclic-AMP Phosphodiesterases,
pubmed-meshheading:10382866-Aflatoxin B1,
pubmed-meshheading:10382866-Animals,
pubmed-meshheading:10382866-Cell Division,
pubmed-meshheading:10382866-Enzyme Inhibitors,
pubmed-meshheading:10382866-Female,
pubmed-meshheading:10382866-Mice,
pubmed-meshheading:10382866-Mutagens,
pubmed-meshheading:10382866-Rats,
pubmed-meshheading:10382866-Rats, Wistar,
pubmed-meshheading:10382866-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
Aflatoxin B1 is an inhibitor of cyclic nucleotide phosphodiesterase activity.
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pubmed:affiliation |
Dipartimento de Biologia Cellulare e dello Sviluppo, Università di Roma La Sapienza, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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