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Colbran Lab

Calmodulin kinase II inhibition disrupts cardiomyopathic effects of enhanced green fluorescent protein.

AUTHORS

Khoo MSMichelle S C , Grueter CE Chad E , Eren M Mesut , Yang J Jinying , Zhang R Rong , Bass MA Martha A , Lwin ST Seint T , Mendes LA Lisa A , Vaughan DE Douglas E , Colbran RJ Roger J , Anderson ME Mark E . Journal of molecular and cellular cardiology. 2008 2 ; 44(2). 405-10

ABSTRACT

Transgenic expression of enhanced green fluorescent protein (eGFP) in myocardium can result in cardiac dysfunction and cardiomyopathy, presumably through toxic effects that disrupt normal cellular signaling. The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is widely expressed in myocardium and CaMKII activity is increased in human and animal models of cardiomyopathy, so we hypothesized that increased CaMKII activity is important for cardiomyopathy due to transgenic expression of eGFP. Here we report that cardiomyocyte-delimited eGFP over-expression causes increased CaMKII activity that predicts left ventricular dilation and dysfunction. On the other hand, transgenic co-expression of a CaMKII inhibitory peptide with eGFP prevents eGFP-mediated left ventricular dilation and dysfunction. These findings suggest that increased CaMKII activity is a critical pathological signal in transgenic cardiomyopathy due to eGFP over-expression.