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Role of PTEN in diabetes mellitus-induced reduction of hypoxic postconditioning-induced protection of cardiomyocytes: the relationship with GSK-3β-mediated mitochondrial apoptotic pathway / 中华麻醉学杂志
Chinese Journal of Anesthesiology ; (12): 108-111, 2017.
Article in Chinese | WPRIM | ID: wpr-505514
ABSTRACT
Objective To evaluate the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in diabetes mellitus-induced reduction of hypoxic postconditioning (HPO)-induced protection of cardiomyocytes and the relationship with glycogen synthase kinase-3β (GSK-3β)-mediated mitochondrial apoptotic pathway.Methods H9c2 cells incubated in high-glucose (30 mmol/L) medium for 24 h were divided into 6 groups (n =5 each) using a random number tablenormoxia group (group N),hypoxia-reoxygenation (H/R) group,group HPO,PTEN gene silencing normoxia group (group P-N),PTEN gene silencing H/R group (group P-H/R),and PTEN gene silencing HPO group (group P-HPO).H9c2 cells were exposed to 95% N2-5% CO2 for 4 h followed by 2 h reoxygenation with 90% O2-10% CO2.HPO was induced by 3 cycles of 5 min reoxygenation followed by 5 min hypoxia before reoxygenation.At the end of reoxygenation,the level of lactate dehydrogenase (LDH) in the supernatant was detected by enzyme-linked immunosorbent assay,the changes in mitochondrial membrane potential (MMP were assessed by JC-1 fluorescence assay,the cell apoptosis was detected by AnnexinV-FITC/PI flow cytometry,and the expression of PTEN and phosphorylated GSK-3β (p-GSK-3β) was determined by Western blot.The JC-1 monomer/polymer ratio and apoptosis rate were calculated.Results Compared with group N,the amount of LDH released,JC-1 monomer/polymer ratio and apoptosis rate were significantly increased,and the expression of PTEN was up-regulated in H/R and HPO groups (P<0.05).There was no significant difference in the parameters mentioned above between group H/R and group HPO (P>0.05).Compared with group HPO,the amount of LDH released,JC-1 monomer/polymer ratio and apoptosis rate were significantly decreased,PTEN expression was down-regulated,and the expression of p-GSK-3β was up-regulated in group P-HPO (P<0.05).Compared with group N,the expression of PTEN was significantly down-regulated,and no significant changes were found in the other parameters mentioned above in group P-N (P>0.05).Compared with group H/R,the expression of PTEN was significantly down-regulated,and no significant changes were found in the other parameters mentioned above in group P-H/R (P>0.05).Conclusion PTEN is involved in diabetes mellitus-induced reduction of HPO-induced protection of cardiomyocytes,and the mechanism is associated with PTEN-induced activation of GSK-3β-modulated mitochondrial apoptotic pathway.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Anesthesiology Year: 2017 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Anesthesiology Year: 2017 Type: Article