KCNJ11 downregulation stimulates cardiac cell apoptosis in myocarditis

Seungmin Choi, Joo Hee Chung, Myung Hee Nam, Eunjung Bang, Jong Bok Seo, Sung Gil Chi

Research output: Contribution to journalArticlepeer-review

Abstract

One of the inflammatory heart diseases, viz. acute myocarditis, occurs due to cardiac cell death. How-ever, the molecular mechanism underlying cell death remains largely unexplored. In this study, we report that the down-regulation of KCNJ11, a central sub-unit 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 proteo-mics analysis of experimental autoimmune myocardi-tis (EAM), we show that the KCNJ11 level marked by decreased, whereas Camk2a expression increased sig-nificantly in EAM tissues by 16 and 20 days, com-pared 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 re-vealed 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 block-ers (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.

Original languageEnglish
Pages (from-to)1106-1112
Number of pages7
JournalCurrent Science
Volume119
Issue number7
DOIs
Publication statusPublished - 2020 Oct 10

Keywords

  • Apoptosis
  • blood glucose lipopolysaccha-
  • cardiac cells
  • myocarditis
  • ride

ASJC Scopus subject areas

  • General

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