SIRT6 suppresses mitochondrial defects and cell death via the NF-κB pathway in myocardial hypoxia/reoxygenation induced injury

Autor: Ming-Yue, Cheng, You-Wei, Cheng, Jun, Yan, Xiao-Qin, Hu, Hui, Zhang, Zhi-Rong, Wang, Qin, Yin, Wei, Cheng
Rok vydání: 2016
Předmět:
Zdroj: American journal of translational research. 8(11)
ISSN: 1943-8141
Popis: The present study explored changes of the SIRT6/NF-κB pathway in myocardial hypoxia/reoxygenation induced injury and the effects on mitochondrial damage and myocardial damage by regulating SIRT6. SIRT6 expression decreased and NF-κB expression increased in H9c2 cells during hypoxic injury. Cell death and mitochondrial defects paralleled mPTP opening, and a decrease in ΔΨm occurred in hypoxic myocytes compared with normoxic control cells in annexin V and propidium iodide staining and TUNEL results. These effects were suppressed in cells overexpressing SIRT6, but reemerged in cells expressing the SIRT6 mutant. We also found that NF-κB p65 increased in both the cytoplasm and nuclei, which could be repressed by SIRT6 overexpression. The expression level of NF-κB was significantly and negatively correlated with the SIRT6 mRNA level. Our data demonstrated that SIRT6/NF-κB changed during hypoxic injury and SIRT6 overexpression averted mitochondrial defects through inhibition of NF-κB in hypoxic H9c2 cells. Activation of SIRT6 may be a potential method for hypoxia/reoxygenation injury therapy.
Databáze: OpenAIRE