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| Mechanisms by which MTMR14 Ameliorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury via PTEN/Akt Signaling Pathway |
| ZHONG Ni'er, YANG Guang, et al |
| Shaanxi Provincial People's Hospital, Shaanxi Xi'an 710068, China |
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Abstract Objective: To investigate the role and mechanism of myotubularin-related protein 14 (MTMR14) in regulating hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. Methods: The mouse cardiomyocytes were cultured under hypoxia for 6 hours followed by reoxygenation of 12 hours to establish the H/R model. Adeno-associated virus mediated gene delivery was used to overexpress MTMR14. Experiments were divided into normoxic group, H/R group, H/R + control AAV group, and H/R + AAV-MTMR14 group, H/R + AAV-MTMR14 + AAV-PTEN group and H/R + AAV-MTMR14 + MK-2206 group. The mRNA expression of MTMR14 was measured by real-time quantitative PCR (RT-qPCR). The protein levels of MTMR14, Bax, Bcl2, Caspase-3, PTEN and Akt were examined by Western blotting. The survival rate of cardiomyocytes was assessed by cell counting kit-8 (CCK-8) assay. Cell injury of cardiomyocytes was determined by lactate dehydrogenase (LDH) cytotoxicity assay. The apoptosis of cardiomyocytes was examined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Results: MTMR14 expression levels were significantly lower in the H/R group compared with the normoxia group (P<0.05). MTMR14 expression levels were significantly increased in the H/R + AAV-MTMR14 group compared with the H/R + control AAV group (P<0.01). The survival rate of cardiomyocytes was significantly higher and apoptosis rate was significantly lower in the H/R + AAV-MTMR14 group compared with the H/R group and the H/R + control AAV group (P<0.01). PTEN protein levels were significantly lower and Akt protein phosphorylation levels were significantly higher in the H/R + AAV-MTMR14 group compared with the H/R group and the H/R + control AAV group (P<0.01). Compared with the H/R + AAV-MTMR14 group, the H/R + AAV-MTMR14 + AAV-PTEN group had significantly higher PTEN protein levels, significantly lower Akt protein phosphorylation levels, and significantly increased apoptosis rate in cardiomyocytes (P<0.01). Compared with the H/R + AAV-MTMR14 group, the H/R + AAV-MTMR14 + MK-2206 group had significantly lower Akt protein phosphorylation levels and significantly increased cardiomyocyte apoptosis rate (P<0.01). Conclusion: MTMR14 ameliorates H/R-induced cardiomyocyte injury through regulation of the PTEN/Akt pathway.
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2023, Vol. 29 
