Response by Zhou et al to Letter Regarding Article, “Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy”
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We thank Drs Karlstaedt and Taegtmeyer for their favorable comments on our recent report demonstrating mitotic catastrophe as a key mechanism of fatal dilated cardiomyopathy in glycogen synthase kinase 3 (GSK-3)–deficient hearts (conditional GSK-3α/β double knockout [DKO]).1 Considering the complex biology of GSK-3 in regulating numerous biological processes and cellular functions, we completely agree with Drs Karlstaedt and Taegtmeyer that there may be additional layer(s) of complexity to be elucidated for the complete understanding of the molecular basis of the observed phenotype. Indeed, our focus on cell cycle regulation and mitotic catastrophe was guided by unbiased microarray analysis.
It is well established that GSK-3 is a central regulator of nutrient and energy homeostasis. In response to the comments of Karlstaedt et al regarding metabolism, now we have examined the metabolic consequences of the complete loss of GSK-3 in adult hearts. As expected, an increased Periodic acid–Schiff–diastase positivity demonstrated enhanced glycogen deposition in the DKO hearts (Online Figure IA). …