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KCNJ11 Downregulation Stimulates Cardiac Cell Apoptosis in Myocarditis


Affiliations
1 Department of Life Sciences, Korea University, Seoul 02841, Korea, Republic of
2 Korea Basic Science Institute, Seoul Center, Seoul 02841, Korea, Republic of
3 Korea Basic Science Institute, Western Seoul Center, Seoul 03759, Korea, Republic of
 

One of the inflammatory heart diseases, viz. acute myocarditis, occurs due to cardiac cell death. However, the molecular mechanism underlying cell death remains largely unexplored. In this study, we report that the down-regulation of KCNJ11, a central subunit of the ATP-sensitive potassium (KATP) channel plays a key role in the reduction of blood glucose, and is involved in apoptosis of cardiac cells. Using proteomics analysis of experimental autoimmune myocarditis (EAM), we show that the KCNJ11 level marked by decreased, whereas Camk2a expression increased significantly in EAM tissues by 16 and 20 days, compared to control tissues. Using 1H-MAS NMR we also show that glucose levels were slightly elevated in EAM tissues. In vitro assays using H9c2 cardiac cells revealed that both lipopolysaccharide (LPS) and high glucose treatment decreased cell viability, in which toxicity was attenuated by treatment with KATP pharmacological openers, but not by the KATP blockers (Gli and 5-HD). Apoptosis induced by LPS or high glucose treatment was suppressed by Ca2+ chelator (BAPTA-AM) treatment. We found that KCNJ11 levels had decreased in cardiac cells by LPS or high glucose treatment, and siRNA-mediated knockdown of KCNJ11 expression further stimulated the LPS- or high glucose-induced apoptosis. Together, our results demonstrate first that KCNJ11 is down-regulated under inflammation and high glucose conditions and its inactivation facilitates cardiac cell apoptosis. We assume that down-regulation of KCNJ11 has an effect on the development of myocarditis.

Keywords

Apoptosis, Blood Glucose Lipopolysaccharide, Cardiac Cells, Myocarditis.
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  • KCNJ11 Downregulation Stimulates Cardiac Cell Apoptosis in Myocarditis

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Authors

Seungmin Choi
Department of Life Sciences, Korea University, Seoul 02841, Korea, Republic of
Joo Hee Chung
Korea Basic Science Institute, Seoul Center, Seoul 02841, Korea, Republic of
Myung-Hee Nam
Korea Basic Science Institute, Seoul Center, Seoul 02841, Korea, Republic of
Eunjung Bang
Korea Basic Science Institute, Western Seoul Center, Seoul 03759, Korea, Republic of
Jong Bok Seo
Korea Basic Science Institute, Seoul Center, Seoul 02841, Korea, Republic of
Sung-Gil Chi
Department of Life Sciences, Korea University, Seoul 02841, Korea, Republic of

Abstract


One of the inflammatory heart diseases, viz. acute myocarditis, occurs due to cardiac cell death. However, the molecular mechanism underlying cell death remains largely unexplored. In this study, we report that the down-regulation of KCNJ11, a central subunit of the ATP-sensitive potassium (KATP) channel plays a key role in the reduction of blood glucose, and is involved in apoptosis of cardiac cells. Using proteomics analysis of experimental autoimmune myocarditis (EAM), we show that the KCNJ11 level marked by decreased, whereas Camk2a expression increased significantly in EAM tissues by 16 and 20 days, compared to control tissues. Using 1H-MAS NMR we also show that glucose levels were slightly elevated in EAM tissues. In vitro assays using H9c2 cardiac cells revealed that both lipopolysaccharide (LPS) and high glucose treatment decreased cell viability, in which toxicity was attenuated by treatment with KATP pharmacological openers, but not by the KATP blockers (Gli and 5-HD). Apoptosis induced by LPS or high glucose treatment was suppressed by Ca2+ chelator (BAPTA-AM) treatment. We found that KCNJ11 levels had decreased in cardiac cells by LPS or high glucose treatment, and siRNA-mediated knockdown of KCNJ11 expression further stimulated the LPS- or high glucose-induced apoptosis. Together, our results demonstrate first that KCNJ11 is down-regulated under inflammation and high glucose conditions and its inactivation facilitates cardiac cell apoptosis. We assume that down-regulation of KCNJ11 has an effect on the development of myocarditis.

Keywords


Apoptosis, Blood Glucose Lipopolysaccharide, Cardiac Cells, Myocarditis.

References





DOI: https://doi.org/10.18520/cs%2Fv119%2Fi7%2F1106-1112