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??의 iNOS 발현과 PKCα 억제를 통한 혈관평활근세포의 apoptosis 유도

Mechanisms of Siegesbeckia Glabrescens-induced Smooth Muscle Cell Apoptosis: Role of iNOS and PKCα

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Abstract

We have recently demonstrated that Siegesbeckia glabrescens(SG), a herbal medicine, induces apoptosis via nitric oxide(NO) production in human aortic smooth muscle cells(HASMCs). However, the molecular pathways involved in SG-mediated apoptosis are not fully understand. In the present study, we investigated the cellular mechanisms of SG-induced apoptosis in HASMCs. SG induced NO production through inducible nitric oxide synthase(iNOS) induction. The apoptotic effect of SG was attenuated by L-NNA, a NOS inhibitor. In the presence of L-NNA, the degradation of procaspase-3 by SG was inhibited. SG treatment induced a decrease in Bcl-2 expression but did not affect the expression of Bax. In addition, SG treatment evoked both down-regulation of PKC α and inhibition of PKC α phosphorylation. These downregulations were reversed by addition of L-NNA. It seems likely to be a downregulation of PKCα due to long term treatment with PMA. Taken together, these results suggest that apoptotic effects of SG may be due to NO production via iNOS mRNA expression. Furthermore, Bcl-2 and PKCα downregulation, and caspase-3 activation may be involved in the mechanisms for apoptotic effects by SG.

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