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A more recent version of this article appeared on December 1, 2006

Papers In Press, published online ahead of print September 16, 2006
J. Lipid Res., doi:10.1194/jlr.M600212-JLR200
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Submitted on May 12, 2006
Revised on September 14, 2006
Accepted on September 15, 2006

Hydroxyeicosatetraenoic acids released through cytochrome P-450 pathway regulate 3T6 fibroblast growth

Diana Nieves and Juan José Moreno

Physiology, University of Barcelona, Barcelona E-08028

Corresponding Author: jjmoreno{at}ub.edu

Eicosanoids participate in the regulation of cellular proliferation. Thus, we observed that prostaglandin E2 interaction with membrane receptors is involved in the control of 3T6 fibroblast growth induced by serum. However, our results suggested that another arachidonic acid (AA) pathway might be implicated in these events. Our results show that 3T6 fibroblast synthesized hydroxyeicosatetraenoic acids (HETEs) such as 12-HETE through cytochrome P450 (CYP450) pathway. However, 3T6 fibroblast did not produce leucotriene B4 and lipoxygenase inhibitors and leukotriene antangonists failed to inhibit 3T6 fibroblast growth induced by FBS. In contrast, we observed that CYP450 inhibitors such as SKF-525A, 17-ODYA, ABT and PPOH reduced 12(S)-HETE levels and 3T6 fibroblast growth and DNA synthesis induced by FBS. The impairment of DNA synthesis and 3T6 fibroblast growth induced by SKF-525A were reverted by exogenous addition of HETEs. Moreover, we reported that 5-HETE, 12(S)-HETE and 15(S)-HETE are mitogenic on 3T6 fibroblast in absence of another growth factor, and this effect was dependent on activation of phosphatidylinositol-3-kinase pathway. In conclusion, our results show that HETEs probably produced by CYP450 are involved in the control of 3T6 fibroblast growth.


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[Abstract] [Full Text] [PDF]


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