title: Novel role of silent information regulator 1 in acute endothelial cell oxidative stress injury.
abstract: Silent information regulator 1 (SIRT1), a class III histone deacetylase, retards aging and plays roles in cellular oxidative stress injury (OSI). However, the biological context in which SIRT1 promotes oxidative injury is not fully understood. Here, we show that SIRT1 essentially mediates hydrogen peroxide (H2O2)-induced cytotoxicity in human umbilical vein endothelial cell (HUVEC). In HUVECs, SIRT1 protein expression was significantly increased in a dose-dependent manner after H2O2 treatment, whereas the acetylation levels of the NF-κB p65 subunit and p53 were decreased. EX527 (a specific SIRT1 inhibitor) conferred protection to the HUVECs against H2O2, as indicated by an improved cell viability, adhesion, an enhanced migratory ability, a decreased apoptotic index, decreased reactive oxygen species (ROS) production and reductions in several biochemical parameters. Immunofluorescence and Western blot analyses demonstrated that H2O2 treatment up-regulated SIRT1, phosphorylated-JNK (p-JNK), p-p38MAPK, and p-ERK expression. EX527 pretreatment reversed these effects on SIRT1, p-JNK, and p-p38MAPK but further increased the p-ERK levels. Similar results were confirmed in SIRT1 siRNA experiments. In summary, SIRT1 signaling pathway inhibition imparts protection against acute endothelial OSI, and modulation of MAPKs (JNK, p38MAPK, and ERK) may be involved in the protective effect of SIRT1 inhibition.
authors.affiliation: Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medical Management, Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an 710038, China; Department of Cardiothoracic Surgery, The 97th Hospital of PLA, 226 Tongshan Road, Xuzhou 221004, China.
authors.forename: Yingtong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an 710038, China.
authors.forename: Chongxi
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Pei
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Stomatology, The 253rd Hospital of PLA, 111 Aimin Road, Hohhot 010051, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China; Department of Medical Administration, Beidaihe Sanatorium, Beijing Military Area Command, 4 West Beach Road, Qinhuangdao 066100, China. Electronic address: yang200214yy@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. Electronic address: yanqu1974@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qu
keywords: Acute oxidative stress injury; EX527; Mitogen activated protein kinases; Silent information regulator 1