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Cardiovasc Diabetol. 2009 Feb 11;8:8. doi: 10.1186/1475-2840-8-8.

The signal transduction pathway of PKC/NF-kappa B/c-fos may be involved in the influence of high glucose on the cardiomyocytes of neonatal rats.

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The Department of Cardiovascular Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR China.



High glucose could induce structure and function change in cardiomyocytes, PKC plays a core effect in the onset and progression of diabetic cardiomyopathy, but its underlying downstream signal transduction pathway is still not completely understood.


To study the influence of high glucose on the structure, function and signal transduction pathway of PKC (Protein Kinase C)/NF-kappaB(Nuclear factor-kappaB)/c-fos in cultured cardiomyocytes.


Using cultured cardiomyocytes of neonatal Sprague-Dawley rats as a model, groups were divided into: control group (glucose: 5 mmol/L); high glucose group (glucose: 10 mmol/L, 15 mmol/L, 20 mmol/L, 25.5 mmol/L); equimolar mannital group (5 mmol/L glucose + 20.5 mmol/L maninital); high glucose(25.5 mmol/L) add PKC inhibitor (Ro-31-8220, 50 nmol/L); high glucose (25.5 mmol/L) add NF-kappaB inhibitor (BAY11-7082, 5 mumol/L). The cellular contracting frequency and volumes were measured and the expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2, NF-kappaB, p-NF-kappaB, TNF-alpha (tumor necrosis factor-alpha) and c-fos were measured by western blot or RT-PCR.


Cardiomyocytes cultured in high glucose level, but not iso-osmotic mannital, showed an increased pulsatile frequency and higher cellular volumes consistent with the increased glucose levels, and also higher expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2, NF-kappaB, p-NF-kappaB, TNF-alpha and c-fos. The addition of Ro-31-8220 and BAY11-7082 could partly reverse these changes induced by high glucose level.


High glucose significantly increased the pulsatile frequency and cellular volumes of cultured cardiomyocytes via PKC/NF-kappaB/c-fos pathway, which might lead to diabetic cardiomyopathy.

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