Document Detail


Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway regulate 3T6 fibroblast growth.
MedLine Citation:
PMID:  16980726     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Eicosanoids participate in the regulation of cellular proliferation. Thus, we observed that prostaglandin E(2) interaction with membrane receptors is involved in the control of 3T6 fibroblast growth induced by serum. However, our results suggested that another arachidonic acid pathway might be implicated in these events. Our results show that 3T6 fibroblasts synthesized hydroxyeicosatetraenoic acids (HETEs) such as 12-HETE through the cytochrome P-450 (CYP450) pathway. However, 3T6 fibroblasts did not produce leukotriene B(4) (LTB(4)), and lipoxygenase inhibitors and LT antagonists failed to inhibit 3T6 fibroblast growth induced by FBS. In contrast, we observed that CYP450 inhibitors such as SKF-525A, 17-octadecynoic acid, 1-aminobenzotriazole, and 6-(2-propargyloxyphenyl)hexanoic acid reduced 12(S)-HETE levels, 3T6 fibroblast growth, and DNA synthesis induced by FBS. The impairment of DNA synthesis and 3T6 fibroblast growth induced by SKF-525A were reversed by exogenous addition of HETEs. Moreover, we report that 5-HETE, 12(S)-HETE, and 15(S)-HETE are mitogenic on 3T6 fibroblast in the absence of another growth factor, and this effect was dependent on the activation of the phosphatidylinositol-3-kinase pathway. In conclusion, our results show that HETEs, probably produced by CYP450, are involved in the control of 3T6 fibroblast growth.
Authors:
Diana Nieves; Juan José Moreno
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-16
Journal Detail:
Title:  Journal of lipid research     Volume:  47     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-20     Completed Date:  2007-01-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2681-9     Citation Subset:  IM    
Affiliation:
Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Animals
Arachidonic Acid / metabolism
Cell Cycle / drug effects
Cell Line
Cell Proliferation / drug effects
Culture Media
Cytochrome P-450 Enzyme System / antagonists & inhibitors,  metabolism*
DNA / biosynthesis
Enzyme Inhibitors / pharmacology
Fibroblasts / cytology*,  drug effects,  metabolism*
Hydroxyeicosatetraenoic Acids / metabolism*,  pharmacology
Leukotriene Antagonists / pharmacology
Lipoxygenase Inhibitors / pharmacology
Mice
Proadifen / pharmacology
Proto-Oncogene Proteins c-akt / metabolism
Chemical
Reg. No./Substance:
0/Culture Media; 0/Enzyme Inhibitors; 0/Hydroxyeicosatetraenoic Acids; 0/Leukotriene Antagonists; 0/Lipoxygenase Inhibitors; 302-33-0/Proadifen; 506-32-1/Arachidonic Acid; 9007-49-2/DNA; 9035-51-2/Cytochrome P-450 Enzyme System; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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


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