Mitochondrial gene COX2 methylation and downregulation is a biomarker of aging in heart mesenchymal stem cells
| Autor: | Dehai Yu, Xiguang Sun, Yudan Lv, Zilong Wang, Xiaoqiang Cong, Li Rong, Tianye Yang, Zhuo Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Senescence senescence Down-Regulation Biology DNA Mitochondrial DNA methyltransferase Gene Expression Regulation Enzymologic Mitochondria Heart Electron Transport Complex IV 03 medical and health sciences 0302 clinical medicine Gene expression Genetics Humans mesenchymal stem cell Cellular Senescence Myocardium Mesenchymal Stem Cells Articles General Medicine Methylation cytochrome c oxidase subunit II DNA Methylation Cell cycle Telomere Cell biology mitochondria 030104 developmental biology 030220 oncology & carcinogenesis DNA methylation methylation Cell aging |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| Popis: | The mitochondria have been proven to be involved in processes of aging; however, the mechansims through which mitoepigenetics affect the cytological behaviors of cardiomyocytes during the aging process are not yet fully understood. In the present study, two senescence models were constructed, replicative senescence (RS) and stress-induced premature senescence (SIPS), using human heart mesenchymal stem cells (HMSCs). First, the differences in age-related gene expression levels and telomere length were compared between the HMSCs in the RS and SIPS models by PCR. Subsequently, protein expression and the mitochondrial DNA (mtDNA) methylation status of cytochrome c oxidase subunit II (COX2) was measured by western blot analysis and bisulfite genomic sequencing (BSP). Finally, the value of the DNA methyltransferase (Dnmt) inhibitor, 5-aza-2′-deoxycytidine (AdC), in delaying the senescence of HMSCs was evaluated. It was found that the p16, p27 and p53 mRNA expression levels increased in the senescent cells, whereas p21 mRNA expression did not. It was also found that telomere shortening only occurred in the RS model, but not in the SIPS model. Along with the senescence of HMSCs, COX2 gene methylation increased and its protein expression level significantly decreased. It was demonstrated that AdC inhibited COX2 methylation and downregulated COX2 expression. The addition of exogenous COX2 or the administration of AdC promoted cell proliferation and delayed cell aging. On the whole, the present study demonstrates that COX2 methylation and downregulation are biomarkers of HMSC senescence. Thus, COX2 may have potential for use as a therapeutic target of cardiovascular diseases and this warrants further investigation. |
| Databáze: | OpenAIRE |
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