Cardiac ankyrin repeat protein attenuates cardiomyocyte apoptosis by upregulation of Bcl-2 expression.

Cardiac ankyrin repeat protein is a nuclear transcriptional co-factor that has additional functions in the myoplasm as a component of the muscle sarcomere. Previous studies have demonstrated increased expression of in cardiovascular diseases, however, its role in cardiomyocyte apoptosis is unclear and controversial. In the present study, we investigated possible roles of Cduanyu37 in hypoxia/reoxygenation (H/R) -induced cardiomyocyte apoptosis and the underlying mechanisms. Neonatal mouse ventricular cardiomyocytes were isolated and infected with adenovirus encoding Flag-tagged Cduanyu37 and lentivirus encoding Cduanyu37 targeted shRNA respectively. Cardiomyocyte apoptosis induced by exposure to H/R conditions was evaluated by TUNEL staining and western blot analysis of cleaved caspase-3. The results showed that H/R-induced apoptosis was significantly decreased in cardiomyocytes and increased in cardiomyocytes, suggesting a protective anti-apoptosis role for Interestingly, over-expressed Cduanyu37 was mainly distributed in the nucleus, consistent with its role in regulating transcriptional activity. qPCR analysis showed that Bcl-2 transcripts were significantly increased in Ad-Cduanyu37 cardiomyocytes. ChIP and co-IP assays confirmed the binding of Cduanyu37 to the Bcl-2 promoter through interaction with transcription factor GATA4. Collectively, our results suggest that Cduanyu37 can protect against H/R induced cardiomyocyte apoptosis, possibly through increasing anti-apoptosis Bcl-2 gene expression.

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