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Blockade of chronic high glucose-induced endothelial apoptosis by Sasa borealis bamboo extract: modulation of NADPH oxidase and heat shock protein

¹ Hallym University

^* To whom correspondence should be addressed. E-mail: yhkang{at}hallym.ac.kr.

	Abstract

Hyperglycemia is a casual factor in the development of diabetic vascular complications including impaired vascular smooth muscle contractility and increased cell proliferation. The present study was designed to investigate effects of Sasa borealis water-extract (SBwE) on chronic hyperglycemia-induced oxidative stress and apoptosis in human umbilical endothelial cells (HUVEC). HUVEC were cultured in 5.5 mM low glucose, 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control, or 33 mM high glucose for 5 d in the absence and presence of 1-30 µ g/mL SBwE. Caspase-3 activation and Annexin V staining revealed that chronic high glucose induced endothelial apoptotic toxicity with a generation of oxidants detected by DCF-fluorescence, and these effects were reversed by SBwE at 1 µ g/mL in a dose-dependent manner. Cytoprotective SBwE substantially reduced the sustained high glucose-induced expression of endothelial nitric oxide synthase, and hence attenuated the formation of peroxynitrite radicals. The suppressing effects of SBwE were most likely mediated through blunting activation of PKC 2 and NADPH oxidase promoted by high glucose. In addition, this bamboo extract modulated the high glucose-triggered MAPK-dependent up-regulation of heat shock proteins. Our results suggest that SBwE suppressed these detrimental effects caused by PKC-dependent peroxynitrite formation via activation of NADPH oxidase and induction of nitric oxide synthase and heat shock protein family that may be essential mechanisms responsible for increased apoptotic oxidative stress in diabetic vascular complications. Moreover, the blockade of high glucose-elicited-heat shock protein induction appeared to be responsible for SBwE-alleviated endothelial apoptosis. Therefore, SBwE may be a therapeutic agent for the prevention and treatment of diabetic endothelial dysfunction and complications.

Key Words: endothelial apoptosis, heat shock protein, high glucose, NADPH oxidase, peroxynitrite, Sasa borealis

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