Resveratrol improves cardiac contractility following trauma-hemorrhage by modulating Sirt1

Bixi Jian, Shaolong Yang, Irshad H. Chaudry, Raghavan Pillai Raju

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Mitochondria play a critical role in metabolic homeostasis of a cell. Our recent studies, based on the reported interrelationship between c-Myc and Sirt1 (mammalian orthologue of yeast sir2 [silent information regulator 2]) expression and their role in mitochondrial biogenesis and function, demonstrated a significant downregulation of Sirt1 protein expression and an upregulation of c-Myc following trauma-hemorrhage (T-H). Activators of Sirt1 are known to improve mitochondrial function and the naturally occurring polyphenol resveratrol (RSV) has been shown to significantly increase Sirt1 activity by increasing its affinity to both NAD + and the acetylated substrate. In this study we tested the salutary effect of RSV following T-H and its influence on Sirt1 expression. Rats were subjected to T-H or sham operation. RSV (8 mg/kg body weight, intravenously) or vehicle was administered 10 min after the onset of resuscitation, and the rats were killed 2 h following resuscitation. Sirtinol, a Sirt1 inhibitor, was administered 5 min prior to RSV administration. Cardiac contractility (±dP/dt) was measured and heart tissue was tested for Sirt1, Pgc-1α, c-Myc, cytosolic cytochrome C expression and ATP level. Left ventricular function, after T-H, was improved (P < 0.05) following RSV treatment, with significantly elevated expression of Sirt1 (P < 0.05) and Pgc-1α (P < 0.05), and decreased c-Myc (P < 0.05). We also observed significantly higher cardiac ATP content, declined cytosolic cytochrome C and decreased plasma tumor necrosis factor-α in the T-H-RSV group. The salutary effect due to RSV was abolished by sirtinol, indicating a Sirt1-mediated effect. We conclude that RSV may be a useful adjunct to resuscitation fluid following T-H.

Original languageEnglish (US)
Pages (from-to)209-214
Number of pages6
JournalMolecular Medicine
Volume18
Issue number2
DOIs
StatePublished - Feb 1 2012

Fingerprint

Hemorrhage
Wounds and Injuries
Resuscitation
Cytochromes
Adenosine Triphosphate
resveratrol
Polyphenols
Organelle Biogenesis
Left Ventricular Function
NAD
Mitochondria
Homeostasis
Up-Regulation
Down-Regulation
Tumor Necrosis Factor-alpha
Yeasts
Body Weight
Proteins
sirtinol

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Resveratrol improves cardiac contractility following trauma-hemorrhage by modulating Sirt1. / Jian, Bixi; Yang, Shaolong; Chaudry, Irshad H.; Raju, Raghavan Pillai.

In: Molecular Medicine, Vol. 18, No. 2, 01.02.2012, p. 209-214.

Research output: Contribution to journalArticle

Jian, Bixi ; Yang, Shaolong ; Chaudry, Irshad H. ; Raju, Raghavan Pillai. / Resveratrol improves cardiac contractility following trauma-hemorrhage by modulating Sirt1. In: Molecular Medicine. 2012 ; Vol. 18, No. 2. pp. 209-214.
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