Inhibition of BMP2K-Inducible Kinase (BMP2K) reduces cardiomyocyte apoptosis
Description
OBJECTIVES: Elevated cardiomyocyte apoptosis is associated with cardiac dysfunction caused by acute myocardial infarction. Therefore, there is a critical need to discover methods to reduce cardiomyocyte apoptosis. Protein kinase dysregulation is related to myocardial ischemia-reperfusion injury. The physiological roles of approximately one-third of the 538 protein kinases encoded by the human genome remain largely uncharacterized. In our laboratory, previous kinome profiling experiments demonstrated that after H9c2 cardiomyocytes were subjected to hypoxia and nutrient deprivation (simulated ischemia) the understudied kinases bone morphogenic protein 2-inducible kinase (BMP2K) and adaptor-associated kinase 1 (AAK1) were activated. Therefore, we tested the hypothesis that inhibition of BMP2K and/or AAK1 would reduce simulated ischemia-induced damage to H9c2 cells.
METHODS: BMP2K and AAK1 activity were inhibited in H9c2 cells using the dual (BMP2K/AAK1) inhibitor (SGC-AAK1-1) and siRNA. The cells were then subjected to simulated ischemia for 4 hours. Cell viability assays and immunoblots were performed to determine cell viability and apoptosis induction, respectively.
RESULTS: Treatment with SGC-AAK1-1 inhibited BMP2K activity, increased cell viability, and reduced the appearance of apoptosis markers. siRNA knockdown experiments demonstrated that reduced expression of BMP2K increased cell viability and reduced apoptosis. In contrast, AAK1 knockdown did not produce significant protective effects.
CONCLUSIONS: Our findings suggest that inhibition of BMP2K, but not AAK1, reduces cellular damage caused by simulated ischemia in the H9c2 cardiomyocyte cell line. Targeting BMP2K may represent a promising therapeutic strategy to reduce cardiac damage following myocardial infarction.
ACKNOWLEDGMENTS: This study was supported by the Des Moines University MSRP and the Des Moines University Iowa Osteopathic Education and Research R&G award #01-25-08.
Citation Information
Sadorf, Blake C. and Wauson, Eric, "Inhibition of BMP2K-Inducible Kinase (BMP2K) reduces cardiomyocyte apoptosis" (2026). Office of Research DMU Research Symposium. 38.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/38
Inhibition of BMP2K-Inducible Kinase (BMP2K) reduces cardiomyocyte apoptosis
OBJECTIVES: Elevated cardiomyocyte apoptosis is associated with cardiac dysfunction caused by acute myocardial infarction. Therefore, there is a critical need to discover methods to reduce cardiomyocyte apoptosis. Protein kinase dysregulation is related to myocardial ischemia-reperfusion injury. The physiological roles of approximately one-third of the 538 protein kinases encoded by the human genome remain largely uncharacterized. In our laboratory, previous kinome profiling experiments demonstrated that after H9c2 cardiomyocytes were subjected to hypoxia and nutrient deprivation (simulated ischemia) the understudied kinases bone morphogenic protein 2-inducible kinase (BMP2K) and adaptor-associated kinase 1 (AAK1) were activated. Therefore, we tested the hypothesis that inhibition of BMP2K and/or AAK1 would reduce simulated ischemia-induced damage to H9c2 cells.
METHODS: BMP2K and AAK1 activity were inhibited in H9c2 cells using the dual (BMP2K/AAK1) inhibitor (SGC-AAK1-1) and siRNA. The cells were then subjected to simulated ischemia for 4 hours. Cell viability assays and immunoblots were performed to determine cell viability and apoptosis induction, respectively.
RESULTS: Treatment with SGC-AAK1-1 inhibited BMP2K activity, increased cell viability, and reduced the appearance of apoptosis markers. siRNA knockdown experiments demonstrated that reduced expression of BMP2K increased cell viability and reduced apoptosis. In contrast, AAK1 knockdown did not produce significant protective effects.
CONCLUSIONS: Our findings suggest that inhibition of BMP2K, but not AAK1, reduces cellular damage caused by simulated ischemia in the H9c2 cardiomyocyte cell line. Targeting BMP2K may represent a promising therapeutic strategy to reduce cardiac damage following myocardial infarction.
ACKNOWLEDGMENTS: This study was supported by the Des Moines University MSRP and the Des Moines University Iowa Osteopathic Education and Research R&G award #01-25-08.
