Enhancement by alpha-tocopheryl hemisuccinate of nitric oxide production induced by lypopolysaccharide and interferon-gamma through the upregulation of protein kinase C in rat vascular smooth muscle cells.
The effect of alpha-tocopheryl hemisuccinate (TS) on lipopolysaccharide (LPS)/interferon-gamma (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 alpha-tocopherol (alpha-T) derivatives alpha-tocopheryl acetate (TA) and alpha-tocopheryl nicotinate (TN), or alpha-T itself. alpha-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 PKCalpha 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.
Kogure
Kentaro
K
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Morita
Motoki
M
Hama
Susumu
S
Nakashima
Sawa
S
Tokumura
Akira
A
Fukuzawa
Kenji
K
D000818:Animals; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D024505:Tocopherols; D015854:Up-Regulation; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D008070:Lipopolysaccharides; D014810:Vitamin E; D009569:Nitric Oxide; D007371:Interferon-gamma; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D024505:Tocopherols