Activation of CaMKIIδC is a common intermediate of diverse death stimuli-induced heart muscle cell apoptosis

Weizhong Zhu, Anthony Yiu Ho Woo, Dongmei Yang, Heping Cheng, Michael T. Crow, Rui Ping Xiao

Research output: Contribution to journalArticle

Abstract

Ca2+-calmodulin-dependent protein kinase II (CaMKII) is expressed in many mammalian cells, with the δ isoform predominantly expressed in cardiomyocytes. Previous studies have shown that inhibition of CaMKII protects cardiomyocytes against β1-adrenergic receptor-mediated apoptosis. However, it is unclear whether activation of CaMKII is sufficient to cause cardiomyocyte apoptosis and whether CaMKII signaling is important in heart muscle cell apoptosis mediated by other stimuli. Here, we specifically enhanced or suppressed CaMKII activity using adenoviral gene transfer of constitutively active (CA-CaMKIIδC) or dominant negative (DN-CaMKIIδC) mutants of CaMKIIδC in cultured adult rat cardiomyocytes. Expression of CA-CaMKIIδC promoted cardiomyocyte apoptosis that was associated with increased mitochondrial cytochrome c release and attenuated by co-expression of Bcl-X L. Importantly, isoform-specific suppression of CaMKII δC with the DN-CaMKIIδC mutant similar to nonselective CaMKII inhibition by the pharmacological inhibitors (KN-93 or AIP) not only prevented CA-CaMKIIδC-mediated apoptosis but also protected cells from multiple death-inducing stimuli. Thus, activation of CaMKIIδC constitutes a common intermediate by which various death-inducing stimuli trigger cardiomyocyte apoptosis via the primary mitochondrial death pathway.

Original languageEnglish (US)
Pages (from-to)10833-10839
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number14
DOIs
StatePublished - Apr 6 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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