US EPA

2307393 

Journal Article 

Abstract 

Heavy metal-mediated lipid signaling in vascular endothelial cells: methylmercury-induced phospholipase D regulation by phospholipase A(2) and eicosanoids 

Sherwai, S; Pabon, S; Kuppusamy, M; Sayyid, M; Kotha, S; Maddipati, K; Parinandi, N 

2008 

Yes 

Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 

45 

Suppl. 

S150-S150 

English 

WOS:000260867900425 

http://www.sciencedirect.com/science/article/pii/S0891584908006321
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is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts

Mercury, especially MeHg, is implicated in the etiology of cardiovascular diseases. Hence, we investigated the mechanism of MeHg-induced phospholipase D (PLD) activation through the upstream regulation of PLA2, cyclooxygenase (COX) and lipoxygenase (LOX) as an underlying lipid signaling mechanism of MeHg-induced endothelial dysfunctions in the bovine pulmonary artery endothelial cells (BPAECs). Our results showed that MeHg significantly activated both PLA2 (as determined by the release of [3H]arachidonic acid, AA) and PLD (by the formation of [32P]phosphatidylbutanol) in BPAECs in a dose- (0 to 10 μM) and time-dependent (0 to 60 min) manner. the cPLA2-specific inhibitor, AACOCF3, significantly attenuated the MeHg-induced [3H]AA release, suggesting that MeHg activated cPLA2 in ECs. Furthermore, the MeHg-induced PLD activation was also inhibited by AACOCF3, indicating that the activation of cPLA2 was upstream of activation of PLD in BPAECs. the COX-specific inhibitors (aspirin, ibuprofen, indomethacin, and nimesulide) and the LOX-specific inhibitors (caffeic acid, ETI, ETYA and baicalein) significantly attenuated the MeHg-induced PLD activation, suggesting that COXs and LOXs were involved in the MeHg induced activation of PLD in ECs. Liquid chromatography-mass spectrometry analysis showed that MeHg also significantly induced the formation of COX- and LOX-catalyzed eicosanoids in ECs, confirming the activation of COXs and LOXs by MeHg. For the first time, we showed that MeHg activated PLD in ECs through the activation of cPLA2 and eicosanoids formed by COXs and LOXs. 

Society for Free Radical Biology and Medicine 15th Annual Meeting 

Indianapolis, IN 

November 19-23, 2008