Nuclear calcium/calmodulin-dependent protein kinase II signaling enhances cardiac progenitor cell survival and cardiac lineage commitment

Pearl Quijada, Nirmala Hariharan, Jonathan D. Cubillo, Kristin M. Bala, Jacqueline M. Emathinger, Bingyan J. Wang, Lucia Ormachea, Donald M Bers, Mark A. Sussman, Coralie Poizat

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Ca2+/Calmodulin-dependent protein kinase II (CaMKII) signaling in the heart regulates cardiomyocyte contractility and growth in response to elevated intracellular Ca2+. The δB isoform of CaMKII is the predominant nuclear splice variant in the adult heart and regulates cardiomyocyte hypertrophic gene expression by signaling to the histone deacetylase HDAC4. However, the role of CaMKIIδ in cardiac progenitor cells (CPCs) has not been previously explored. During post-natal growth endogenous CPCs display primarily cytosolic CaMKIIδ, which localizes to the nuclear compartment of CPCs after myocardial infarction injury. CPCs undergoing early differentiation in vitro increase levels of CaMKIISB in the nuclear compartment where the kinase may contribute to the regulation of CPC commitment. CPCs modified with lentiviral-based constructs to overexpress CaMKIIδB (CPCeδB) have reduced proliferative rate compared with CPCs expressing eGFP alone (CPCe). Additionally, stable expression of CaMKIIδB promotes distinct morphological changes such as increased cell surface area and length of cells compared with CPCe. CPCeδB are resistant to oxidative stress induced by hydrogen peroxide (H2O2) relative to CPCe, whereas knockdown of CaMKIISB resulted in an upregulation of cell death and cellular senescence markers compared with scrambled treated controls. Dexamethasone (Dex) treatment increased mRNA and protein expression of cardiomyogenic markers cardiac troponin T and α-smooth muscle actin in CPCeSB compared with CPCe, suggesting increased differentiation. Therefore, CaMKIIδB may serve as a novel modulatory protein to enhance CPC survival and commitment into the cardiac and smooth muscle lineages.

Original languageEnglish (US)
Pages (from-to)25411-25426
Number of pages16
JournalJournal of Biological Chemistry
Issue number42
StatePublished - Oct 16 2015

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology


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