TAILIEUCHUNG - Báo cáo Y học: Enhancement by a-tocopheryl hemisuccinate of nitric oxide production induced by lypopolysaccharide and interferon-c through the upregulation of protein kinase C in rat vascular smooth muscle cells

The effect of a-tocopheryl hemisuccinate (TS) on lipopolysaccharide (LPS)/interferon-c (IFN)-induced nitric oxide production in rat vascular smooth muscle cells (VSMC) was examined. The LPS/IFN-induced NO production was enhanced by TS but not by the other a-tocopherol (a-T) derivatives a-tocopheryl acetate (TA) and a-tocopheryl nicotinate (TN), or a-T itself. a-T, TA and TN inhibited the enhancement by TS of LPS/IFNinduced NO production. The enhancing effect of TS was observed in the presence of LPS, but not IFN, suggesting that TS participates in the LPS-stimulated signal pathway leading to NO production | Eur. J. Biochem. 269 2367-2372 2002 FEBS 2002 doi Enhancement by a-tocopheryl hemisuccinate of nitric oxide production induced by lypopolysaccharide and interferon-c through the upregulation of protein kinase C in rat vascular smooth muscle cells Kentaro Kogure Motoki Morita Susumu Hama Sawa Nakashima Akira Tokumura and Kenji Fukuzawa1 Faculty of Pharmaceutical Sciences University of Tokushima Japan The effect of a-tocopheryl hemisuccinate TS on lipopolysaccharide LPS interferon-y IFN -induced nitric oxide production in rat vascular smooth muscle cells VSMC was examined. The LPS IFN-induced NO production was enhanced by TS but not by the other a-tocopherol a-T derivatives a-tocopheryl acetate TA and a-tocopheryl nicotinate TN or a-T itself. a-T TA and TN inhibited the enhancement by TS of LPS IFN-induced NO production. The enhancing effect of TS was observed in the presence of LPS but not IFN suggesting that TS participates in the LPS-stimulated signal pathway leading to NO production. Protein kinase C PKC inhibitors but not protein kinase A inhibitors inhibited the enhancing effect of TS on LPS IFN-induced NO production. Furthermore TS enhanced the amount of PKCa in VSMC. From these results we concluded that the enhancing effect of LPS IFN-induced NO production was caused by upregulation of PKC in VSMC. Keywords a-tocopheryl hemisuccunate a-tocopherol nitric oxide vascular smooth muscle cells protein kinase C. The nonantioxidant function of a-tocopherol a-T has been proposed 1-6 . It has been reported that a-T nonanti-oxidatively prevented the proliferation of smooth muscle cells through inhibition of protein kinase C PKC and the transcription of some genes such as CD36 and collagenase. We are interested in a-tocopheryl hemisuccinate TS as a key compound for clarification of the nonantioxidant function of a-T. TS is a naturally occurring amphiphilic compound initially isolated from a green barley extract that stimulates release of

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