Abstract
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.
Highlights
The capacity of the adult mammalian heart to regenerate following injury is severely limited [1,2,3].The myocardial mass of the heart is 70% cardiomyocytes, the contractile units of the heart, which withdraw from the cell cycle during postnatal growth [4,5]
PIM1 regulates c-Kit expression in hematopoietic stem cells [24], but this relationship has not been examined in the myocardial context
PIM1 hearts displayed significantly elevated c-Kit expression compared to non-transgenic (NTg) hearts (Figure 1a and Figure S1a), whereas PIM3 triple knockout (PIM-triple knockout (TKO)) hearts displayed significantly lower c-Kit expression compared to NTg (Figure 1b and Figure S1b)
Summary
The myocardial mass of the heart is 70% cardiomyocytes, the contractile units of the heart, which withdraw from the cell cycle during postnatal growth [4,5]. Pathologic injury, such as myocardial infarction (MI), causes extensive cardiomyocyte death and compromised cardiac function. Enhancing cardiomyocyte survival represents an important strategy for blunting myocardial deterioration and cardiac failure following pathological damage. The cardioprotective role of PIM1 serine threonine kinase (Proviral Insertion site in Murine leukemia virus (PIM) kinase 1) has been extensively studied [7,8,9,10]. PIM1 regulates many cellular processes crucial for antagonizing cellular senescence including cell cycle progression, survival signaling, anti-apoptotic signaling, preservation of mitochondrial integrity, telomere preservation, and blunting of pathological hypertrophy [8,9,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
