Protective effect of lncRNA CRNDE on myocardial cell apoptosis in heart failure by regulating HMGB1 cytoplasm translocat

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Online ISSN 1976-3786 Print ISSN 0253-6269

RESEARCH ARTICLE

Protective effect of lncRNA CRNDE on myocardial cell apoptosis in heart failure by regulating HMGB1 cytoplasm translocation through PARP‑1 Hui Chen1 · Jinming Liu1 · Bin Wang1 · Yongjun Li1   

Received: 13 May 2020 / Accepted: 16 November 2020 © The Pharmaceutical Society of Korea 2020

Abstract  Long non-coding RNAs (lncRNAs) are bound up with the regulation of various diseases. Here, we probed into the effect of lncRNA colorectal neoplasia differentially expressed (CRNDE) on heart failure (HF). The pathological alterations and cell apoptosis of heart tissues were observed by hematoxylin–eosin and TUNEL staining. The viability or apoptosis of mouse myocardial cells HL-1 was tested by XTT or flow cytometry. The interaction between lncRNA CRNDE and poly-ADP-ribose polymerase 1 (PARP-1) was verified by RNA immunoprecipitation and RNA pull-down. The stability of the PARP-1 protein and the acetylation level of high mobility group box-1 (HMGB1) were determined by cycloheximide-chase and immunoprecipitation, respectively. LncRNA CRNDE expression was decreased in HF mice tissues and doxorubicin (Dox)-treated HL-1 cells, whereas PARP-1 and HMGB1 were increased. The overexpression of lncRNA CRNDE restrained HL-1 cell apoptosis induced by Dox. Moreover, the interaction between CRNDE and PARP-1 was corroborated, CRNDE negatively regulated PARP-1 expression, and the overexpression of CRNDE reduced PARP-1 protein stability. In HL-1 cells, PARP-1 positively regulated the acetylation level and cytoplasm translocation of HMGB1. CRNDE restrained Dox-induced apoptosis in mouse myocardial cells via the PARP-1/ HMGB1 pathway. Keywords  LncRNA CRNDE · Myocardial cell · HF · HMGB1 · PARP-1 * Yongjun Li [email protected] 1



Department of Cardiology, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang 050000, Hebei Province, China

Introduction Heart failure (HF) is a heart disease caused by numerous factors and is mainly characterized by systolic and diastolic dysfunction and is an important cause of death in patients with heart diseases (Vucicevic et  al. 2018). Myocardial cells are the basic unit of cardiac contraction and relaxation, indicating that the contractile function of the heart and the apoptosis of myocardial cells have key functions in the pathogenesis of HF (Jose Corbalan et al. 2016). Therefore, examining the mechanism of myocardial cell apoptosis in HF is important to relieve HF. Long noncoding RNAs (lncRNAs) are a class of transcripts that are longer than 200 nucleotides and they regulate gene expression at the epigenetic, translation, or transcription level (Kim and Kook 2019; Park and Han 2019; Heo et al. 2019). LncRNA colorectal neoplasia differentially expressed (CRNDE) is a lncRNA derived from the hCG_1815491 site on chromosome 16 and located on a strand opposite to the adjacent IRX5 gene (Graham et al. 2011). Previous studies have expounded that the overexpression of CRNDE abates cardiac fibrosis and stren