Date of Award
2011
Degree Type
Thesis
Degree Name
Master of Science
Program
Pathology
Supervisor
Dr. Tianqing Peng
Second Advisor
Dr. Subrata Chakrabarti
Abstract
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.
Recommended Citation
Iftekhar, Amina, "SIRT1 signalling promotes lipopolysaccharide-induced TNF-a expression in cardiomyocytes" (2011). Digitized Theses. 3510.
https://ir.lib.uwo.ca/digitizedtheses/3510