RGD Reference Report - Resveratrol improves cardiac contractility following trauma-hemorrhage by modulating Sirt1. - Rat Genome Database

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Resveratrol improves cardiac contractility following trauma-hemorrhage by modulating Sirt1.

Authors: Jian, B  Yang, S  Chaudry, IH  Raju, R 
Citation: Jian B, etal., Mol Med. 2012 Mar 27;18:209-14. doi: 10.2119/molmed.2011.00365.
RGD ID: 7240568
Pubmed: PMID:22113495   (View Abstract at PubMed)
PMCID: PMC3320138   (View Article at PubMed Central)
DOI: DOI:10.2119/molmed.2011.00365   (Journal Full-text)

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-1alpha, 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-1alpha (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-alpha 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hemorrhagic Shock treatmentISOMyc (Rattus norvegicus)7240568; 7240568 RGD 
Hemorrhagic Shock treatmentIDA 7240568 RGD 
Hemorrhagic Shock treatmentISOSirt1 (Rattus norvegicus)7240568; 7240568 RGD 
Hemorrhagic Shock treatmentIMP 7240568 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of heart rate  IMP 7240568 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Myc  (MYC proto-oncogene, bHLH transcription factor)
Sirt1  (sirtuin 1)

Genes (Mus musculus)
Myc  (myelocytomatosis oncogene)
Sirt1  (sirtuin 1)

Genes (Homo sapiens)
MYC  (MYC proto-oncogene, bHLH transcription factor)
SIRT1  (sirtuin 1)


Additional Information