alpha-Lipoic acid activates dimethylarginine dimethylaminohydrolase in cultured endothelial cells

作者：Lee Woo Je; Kim Seung Hwan; Kim Geun Hyang; Han Sung Min; Won Jong Chul; Jung Chang Hee; Park Hye Sun; Choi Do Sook; Lee Ki Up; Park Joong Yeol^*

来源：Biochemical and Biophysical Research Communications, 2010, 398(4): 653-658.

DOI：10.1016/j.bbrc.2010.06.127

• ADMA
• alpha-Lipoic acid
• DDAH
• Endothelial cell
• STAT3

Asymmetric dimethylarginine (ADMA) is a risk factor of cardiovascular diseases, alpha-Lipoic acid (ALA) was shown to improve vascular dysfunction, and to decrease plasma ADMA level. In this study, we investigated whether ALA activates dimethylarginine dimethylaminohydrolase (DDAH), the metabolizing enzyme of ADMA, in cultured endothelial cells. ALA significantly decreased ADMA level in culture media of endothelial cells. ALA increased the gene expression and activity of DDAH, and signal transducer and activator of transcription (STAT)3 phosphorylation. Transfection of STAT3 increased DDAH II promoter activity, and ALA amplified it. ALA-induced increase in DDAH II promoter activity was attenuated in the promoter that had mutation in putative STAT3-binding site. These results suggest that ALA reduces ADMA level by enhancing DDAH activity and DDAH II gene expression, thus providing a novel mechanism by which ALA regulates endothelial function.

• 出版日期2010-8-6