Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells

作者: Zoltan Ungvari , Nazar Labinskyy , Partha Mukhopadhyay , John T. Pinto , Zsolt Bagi

DOI: 10.1152/AJPHEART.00375.2009

关键词: Superoxide dismutaseCell biologyInternal medicineResveratrolBiologyDownregulation and upregulationOxidative stressMitochondrionSirtuin 1Reactive oxygen speciesEndocrinologyEndothelial stem cell

摘要: The production of hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) is a key event in the development diabetic complications. Because resveratrol, naturally occurring polyphenol, has been reported to confer vasoprotection, improving endothelial function and preventing complications diabetes, we investigated effect resveratrol on mtROS cultured human coronary arterial cells (CAECs). measurement MitoSox fluorescence showed that attenuates both steady-state high glucose (30 mM)-induced CAECs, an was prevented by knockdown protein deacetylase silent information regulator 2/sirtuin 1 (SIRT1), intracellular target resveratrol. An overexpression SIRT1 mimicked effects attenuating production. Similar results were obtained CAECs transfected with mitochondria-targeted H2O2-sensitive HyPer-Mito fluorescent sensor. Amplex red assay significantly reduced cellular H2O2 levels as well. Resveratrol upregulated MnSOD expression increased GSH content concentration-dependent manner (measured HPLC coulometric analysis). These attenuated overexpression. We propose via pathway involves activation upregulation antioxidant defense mechanisms, production, suggesting potential for new treatment approaches targeting mitochondria metabolic diseases.

参考文章(102)
João Pedro de Magalhães, Species Selection in Comparative Studies of Aging and Antiaging Research Handbook of Models for Human Aging. pp. 9- 20 ,(2006) , 10.1016/B978-012369391-4/50003-5
James N. Sampayo, Anders Olsen, Gordon J. Lithgow, Oxidative stress in Caenorhabditis elegans: protective effects of superoxide dismutase/catalase mimetics. Aging Cell. ,vol. 2, pp. 319- 326 ,(2003) , 10.1046/J.1474-9728.2003.00063.X
Holly Van Remmen, Arlan Richardson, Oxidative damage to mitochondria and aging Experimental Gerontology. ,vol. 36, pp. 957- 968 ,(2001) , 10.1016/S0531-5565(01)00093-6
Takeshi Nishikawa, Diane Edelstein, Xue Liang Du, Sho-ichi Yamagishi, Takeshi Matsumura, Yasufumi Kaneda, Mark A. Yorek, David Beebe, Peter J. Oates, Hans-Peter Hammes, Ida Giardino, Michael Brownlee, Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage Nature. ,vol. 404, pp. 787- 790 ,(2000) , 10.1038/35008121
Francesco Addabbo, Brian Ratliff, Hyeong-Cheon Park, Mei-Chuan Kuo, Zoltan Ungvari, Anna Ciszar, Boris Krasnikof, Komal Sodhi, Fung Zhang, Alberto Nasjletti, Michael S. Goligorsky, The Krebs Cycle and Mitochondrial Mass Are Early Victims of Endothelial Dysfunction The American Journal of Pathology. ,vol. 174, pp. 34- 43 ,(2009) , 10.2353/AJPATH.2009.080650
Anna Csiszar, Nazar Labinskyy, Xiangmin Zhao, Furong Hu, Sabrina Serpillon, Zhishan Huang, Praveen Ballabh, Richard J. Levy, Thomas H. Hintze, Michael S. Wolin, Steven N. Austad, Andrej Podlutsky, Zoltan Ungvari, Vascular superoxide and hydrogen peroxide production and oxidative stress resistance in two closely related rodent species with disparate longevity. Aging Cell. ,vol. 6, pp. 783- 797 ,(2007) , 10.1111/J.1474-9726.2007.00339.X
Jacob Villegas, Michael McPhaul, Establishment and Culture of Human Skin Fibroblasts Current protocols in molecular biology. ,vol. 71, ,(2005) , 10.1002/0471142727.MB2803S71