Document Type
Article
Publication Date
7-21-2021
Abstract
Aging augments postischemic apoptosis via incomplete mechanisms. Our previous animal study suggests that in addition to proapoptotic effects, lncRNAs also exert antiapoptotic effects in cardiomyocytes. However, whether this unexpected phenomenon exists in humans is unknown. In the present study, we investigated the relationship between aging and apoptosis regulation in human blood samples and confirmed their role by utilizing the cardiomyocyte lines (AC16 cells). Human blood samples were collected from 20 pairs of older adult and young volunteers. Age-different apoptotic regulatory lncRNAs and miRNAs were identified by microarray and bioinformatics analysis. The results indicated that lncRNA (NONHSAT069381 and NONHSAT140844) and miRNA (hsa-miR-124-5p and hsa-miR-6507-5p) were increased in aging human blood, confirmed by both bioinformatics analysis and polymerase chain reaction (PCR). Overexpression of NONHSAT069381 in AC16 cells increased caspase-3 levels and increased cardiomyocyte apoptotic cell death (determined by TUNEL staining and caspase activity assays) after hypoxia/reoxygenation (H/R), while overexpression of NONHSAT140844 increased X-chromosome-linked inhibitor of apoptosis protein (XIAP) content and decreased the myocardial apoptotic cell death. Furthermore, luciferase reporter assay revealed that hsa-miR-124-5p might be a mediator between NONHSAT069381 and mCASP3 and hsa-miR-6507-5p might be a mediator between NONHSAT140844 and mXIAP. Overexpression of hsa-miR-124-5p decreased caspase-3 levels and overexpression of hsa-miR-6507-5p decreased XIAP content in AC16 cells. We have found evidence that lncRNAs are important regulatory molecules in aging-mediated effects upon apoptosis. More interestingly, besides apoptosis-promoting effects, aging also inhibits myocardial apoptosis after H/R. This phenomenon also exists in the human cardiomyocyte line.
Recommended Citation
Zhao, Jinyang; Lin, Xiaolong; Sun, Haoxuan; Zhao, Donghui; Ma, Qin; Lau, Wayne Bond; Cheng, Zichao; Li, Fanqi; Liu, Jinghua; and Fan, Qian, "lncRNA NONHSAT069381 and NONHSAT140844 Increase in Aging Human Blood, Regulating Cardiomyocyte Apoptosis." (2021). Department of Emergency Medicine Faculty Papers. Paper 161.
https://jdc.jefferson.edu/emfp/161
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
34336120
Language
English
Comments
This article is the author's final published version in Oxidative Medicine and Cellular Longevity, July 2021, Article number 9465300
The published version is available at https://doi.org/10.1155/2021/9465300
Copyright © 2021 Jinyang Zhao et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.