Insulin regulates myocardial protection and heat shock proteins through multiple signaling pathways.
Date
2007
Authors
Li, Gefeng.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
In cardiac surgery, insulin is used to improve heart function before and after cardioplegia or ischemic injury. In my experiments I examined several possible molecular mechanisms for the insulin induced myocardial protection. Rat hearts were examined for function and expression of heat shock proteins at 1 and 6 hrs after a single bolus of insulin injected intramuscularly. Indeed, the contractile recovery of hearts after 30 min of global ischemia was significantly improved at 1 and 6 hrs after insulin treatment. While insulin induced expression of Hsp70, this expression was not through the myocardial nitric oxide-cyclic guanosine monophosphate signaling pathway. The insulin-induced myocardial protection at 1 hr after insulin treatment was associated with phosphorylation of Hsp27. Treatment of rats with SB203580, an inhibitor of p38 MAPK, blocked the insulin induced phosphorylation of Hsp27 and the improved myocardial contractile recovery. This suggests that at 1 hr after insulin treatment, the phosphorylation of Hsp27 and the improved myocardial contractile recovery is mainly through insulin stimulation of the p38 MAPK pathway. At 6 hrs after insulin treatment, the heat shock transcription factor (HSF1) was activated, binding to the heat shock element of the promoter region of HS genes. At 6 hrs after insulin treatment, Hsp70 was detected at elevated levels in the hearts and was co-localized with dystrophin to cardiomyocytes membranes. This latter finding is in contrast to the localization of Hsp70 to small blood vessels after heat shock treatment. These results suggest that at 1 and 6 hr after insulin treatment the myocardial protection may be due to stimulation of more than one signaling pathway, and possibly localization of Hsp70 to vulnerable areas of cardiomyocytes. It may be that inducible endogenous myocardial protection as seen after insulin treatment (and after heat shock treatment) is temporally due to multiple signaling pathways and mechanisms.
Thesis (Ph.D.)--Dalhousie University (Canada), 2007.
Thesis (Ph.D.)--Dalhousie University (Canada), 2007.
Keywords
Biology, Molecular.