Abstract |
The 12(S)-lipoxygenase (12-LOX) pathway of arachidonic acid (AA) metabolism after dioxygenation to 12(S)-hydroperoxy-eicosatetraenoic acid is bifurcated in a reduction route to formation of 12(S)-hydroxy-eicosatetraenoic acid (12-HpETE) and an isomerization route to formation of hepoxilins. Interestingly, we found that the rat insulinoma RINm5F cells, which are devoid of cytoplasmic glutathione peroxidase (cGPx)/ phospholipid hydroperoxide glutathione peroxidase (PHGPx), produce solely hepoxilin A(3) (HXA(3)). Since HXA(3) synthesis was abolished in heat-denatured or cGPx- or PHGPx-transfected cells, it was tempting to speculate that a HXA(3) synthase activity regulated by cGPx/PHGPx is present. To confirm this assumption we incubated AA with HeLa cells overexpressing the rat leukocyte-type 12-LOX. Neither HXA(3) nor 12(S)-HETE were detected due to abundance of cGPx/PHGPx. But, pretreatment of transfected cells with diethyl maleate, an inhibitor of glutathione and PHGPx, restored HXA(3) synthase and 12-LOX activities. Thus, we conclude, that cells containing rat leukocyte-type 12-LOX also possess an intrinsic HXA(3) synthase activity, which is activated by inhibition of cGPx/PHGPx. In normal cells HXA(3) is down-regulated by cGPx/PHGPx, but, it is persistently activated in oxidatively stressed cells deficient in cGPx/PHGPx, such as RINm5F.
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Authors | Pattabhiraman Shankaranarayanan, Roberto Ciccoli, Santosh Nigam |
Journal | FEBS letters
(FEBS Lett)
Vol. 538
Issue 1-3
Pg. 107-12
(Mar 13 2003)
ISSN: 0014-5793 [Print] England |
PMID | 12633862
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 11-glutathionylhepoxilin A3
- Glutathione Peroxidase
- Arachidonate 12-Lipoxygenase
- Intramolecular Oxidoreductases
- hepoxilin synthase
- 8,11,14-Eicosatrienoic Acid
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Topics |
- 8,11,14-Eicosatrienoic Acid
(analogs & derivatives, metabolism)
- Animals
- Arachidonate 12-Lipoxygenase
(metabolism)
- Chromatography, High Pressure Liquid
- Gas Chromatography-Mass Spectrometry
- Glutathione Peroxidase
(metabolism)
- Humans
- Insulinoma
(enzymology, metabolism, pathology)
- Intramolecular Oxidoreductases
(metabolism)
- Rats
- Tumor Cells, Cultured
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