title: SIRT6 suppresses mitochondrial defects and cell death via the NF-κB pathway in myocardial hypoxia/reoxygenation induced injury.
abstract: 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.
authors.affiliation: Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou Medical University Jiangsu Province, China.
authors.forename: Ming-Yue
authors.initials: MY
authors.lastname: Cheng
authors.affiliation: Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou Medical University Jiangsu Province, China.
authors.forename: You-Wei
authors.initials: YW
authors.lastname: Cheng
authors.affiliation: Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou Medical University Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou Medical University Jiangsu Province, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Hu
authors.affiliation: Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou Medical University Jiangsu Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou Medical University Jiangsu Province, China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou Medical University Jiangsu Province, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Affiliated Hospital of Xuzhou Medical University, Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou Medical University Jiangsu Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
keywords: NF-κB; SIRT6; hypoxia/reoxygenation; mitochondrial