Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells

Zoltan Ungvari, Nazar Labinskyy, Partha Mukhopadhyay, John T. Pinto, Zsolt Bagi, Praveen Ballabh, Cuihua Zhang, Pal Pacher, Anna Csiszar

Research output: Contribution to journalArticle

217 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number5
DOIs
StatePublished - Nov 1 2009

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Sirtuin 1
Oxidative Stress
Endothelial Cells
Reactive Oxygen Species
Diabetes Complications
Mitochondria
resveratrol
Metabolic Diseases
Polyphenols
Hyperglycemia
Up-Regulation
Antioxidants
Fluorescence
High Pressure Liquid Chromatography
Glucose

Keywords

  • Histone deacetylase
  • Sirtuin 1
  • Vasoprotection

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. / Ungvari, Zoltan; Labinskyy, Nazar; Mukhopadhyay, Partha; Pinto, John T.; Bagi, Zsolt; Ballabh, Praveen; Zhang, Cuihua; Pacher, Pal; Csiszar, Anna.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 297, No. 5, 01.11.2009.

Research output: Contribution to journalArticle

Ungvari, Zoltan ; Labinskyy, Nazar ; Mukhopadhyay, Partha ; Pinto, John T. ; Bagi, Zsolt ; Ballabh, Praveen ; Zhang, Cuihua ; Pacher, Pal ; Csiszar, Anna. / Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. In: American Journal of Physiology - Heart and Circulatory Physiology. 2009 ; Vol. 297, No. 5.
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