Date of Award


Degree Type


Degree Name

Master of Science




Dr. Tianqing Peng

Second Advisor

Dr. Subrata Chakrabarti


Excessive production of TNF-a cytokine by cardiomyocytes in response to lipopolysaccharides (LPS) contributes to myocardial depression during sepsis. However, the exact mechanism by which TNF-a is produced in cardiomyocytes is partly understood. This study investigated the role of Sirtuinl (SIRT1) in LPS-induced TNF-a expression in cardiomyocytes.

LPS increased SIRT1 activity in cultured mice cardiomyocytes. Knockdown of SIRT1 gene reduced TNF-a synthesis in LPS treated cells. Inhibition of SIRT1 reduced TNF-a mRNA and protein, whereas activation of SIRT1 enhanced TNF-a mRNA and protein in LPS stimulated cells. SIRT1 signalling was also associated with activation of NF-kB transcription factor. Further, in vivo study demonstrated that TNF-a mRNA and protein levels were significantly lower in SIRT1 knockout mice compared to wild-type mice during endotoxemia. Results suggest that SIRT1 induces TNF-a expression in LPS stimulated cardiomyocytes through NF-kB activation. Therefore, targeting SIRT1 signalling may be therapeutically significant in minimizing myocardial depression in septic hearts.



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