Inhibition of lncRNA Neat1 by catalpol via suppressing transcriptional activity of NF-κB attenuates cardiomyocyte apoptosis

Cell Cycle. 2019 Dec;18(24):3432-3441. doi: 10.1080/15384101.2019.1673619. Epub 2019 Nov 17.

Abstract

Oxidative stress is considered as a major pathogenesis in myocardial damage; however, effective therapies are limited so far. The present study aimed to investigate the in vitro antioxidative mechanism of Catalpol in cardiomyocytes. The results indicated that Catalpol attenuated high glucose (HG)-induced apoptosis in mouse cardiomyocytes via significantly downregulating long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (Neat1) expression. Furthermore, Catalpol downregulated Neat1 expression and attenuated apoptosis by inhibiting production of intracellular reactive oxygen species (ROS) in HG-treated cardiomyocytes. Moreover, Catalpol also suppressed HG-induced degradation of IκBα and the nuclear localization of nulear factor-κB (NF-κB) by decreasing the intracellular ROS levels. Additionally, chromatin immunoprecipitation (ChIP) and dual-luciferase activity assays validated that NF-κB bound to Neat1 promoter to activate Neat1 expression. In summary, these results implied that Catalpol protected mouse cardiomyocytes against oxidative injury at least partly through ROS-NF-κB-Neat1 axis.

Keywords: Cardiomyocytes; Catalpol; NF-κB; Neat1; oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Gene Expression Regulation / drug effects
  • Glucose / pharmacology
  • Humans
  • Iridoid Glucosides / pharmacology*
  • Mice
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • NF-KappaB Inhibitor alpha / genetics*
  • NF-kappa B / genetics
  • Oxidative Stress / drug effects
  • Promoter Regions, Genetic / drug effects
  • RNA, Long Noncoding / genetics*
  • Reactive Oxygen Species / metabolism
  • Transcription, Genetic / drug effects

Substances

  • Iridoid Glucosides
  • NEAT1 long non-coding RNA, mouse
  • NF-kappa B
  • RNA, Long Noncoding
  • Reactive Oxygen Species
  • NF-KappaB Inhibitor alpha
  • catalpol
  • Glucose

Grants and funding

This study was funded by Supporting Plan for Excellent Innovative Talents of Heilongjiang University of Traditional Chinese Medicine; Heilongjiang Post-doctoral Research Initiation Fund; Two-class and Superiority Discipline Construction Project [051022].