PIM1 Promotes Survival of Cardiomyocytes by Upregulating c-Kit Protein Expression

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 9; p. 2001
• Main Authors: Ebeid, David E, Firouzi, Fareheh, Esquer, Carolina Y, Navarrete, Julian M, Wang, Bingyan J, Gude, Natalie A, Sussman, Mark A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.08.2020; MDPI
• Subjects: AKT protein; Animals; Antibodies; Apoptosis; c-Kit; c-Kit protein; Cardiac function; cardiomyocyte; Cardiomyocytes; cardioprotection; Cell cycle; Cell proliferation; Cell survival; Coronary vessels; Extracellular signal-regulated kinase; Gene expression; Genetic aspects; Health aspects; Heart attacks; Heart cells; Hematopoietic stem cells; Humans; Immunoprecipitation; Insertion; Kinases; KIT protein; Laboratory animals; Mice; Mice, Transgenic; Myocytes, Cardiac - metabolism; Oxidative stress; Phosphatase; Phosphorylation; PIM1; Protein-serine/threonine kinase; Protein-tyrosine kinase receptors; Proteins; Proto-Oncogene Proteins c-kit - metabolism; Proto-Oncogene Proteins c-pim-1 - biosynthesis; Proto-Oncogene Proteins c-pim-1 - genetics; Proto-Oncogene Proteins c-pim-1 - metabolism; Receptor mechanisms; Senescence; Stem cell factor; Stem cell transplantation; Stem cells; Structure-function relationships; Transgenic animals; Up-Regulation; United States; United States > US; PIM1; cardioprotection; c-Kit; cardiomyocyte
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9092001

Enhancing cardiomyocyte survival is crucial to blunt deterioration of myocardial structure and function following pathological damage. PIM1 (Proviral Insertion site in Murine leukemia virus (PIM) kinase 1) is a cardioprotective serine threonine kinase that promotes cardiomyocyte survival and antagonizes senescence through multiple concurrent molecular signaling cascades. In hematopoietic stem cells, PIM1 interacts with the receptor tyrosine kinase c-Kit upstream of the ERK (Extracellular signal-Regulated Kinase) and Akt signaling pathways involved in cell proliferation and survival. The relationship between PIM1 and c-Kit activity has not been explored in the myocardial context. This study delineates the interaction between PIM1 and c-Kit leading to enhanced protection of cardiomyocytes from stress. Elevated c-Kit expression is induced in isolated cardiomyocytes from mice with cardiac-specific overexpression of PIM1. Co-immunoprecipitation and proximity ligation assay reveal protein-protein interaction between PIM1 and c-Kit. Following treatment with Stem Cell Factor, PIM1-overexpressing cardiomyocytes display elevated ERK activity consistent with c-Kit receptor activation. Functionally, elevated c-Kit expression confers enhanced protection against oxidative stress in vitro. This study identifies the mechanistic relationship between PIM1 and c-Kit in cardiomyocytes, demonstrating another facet of cardioprotection regulated by PIM1 kinase.