机构：[a]The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China[b]Institute of Neuroscience, Soochow University, Suzhou, China[c]Department of Surgery, The Third Hospital Affiliated to Soochow University, Changzhou City, Jiangsu, 213003, China[d]Changshu Entry-Exit Inspection and Quarantine Bureau, Changshu, China[e]The Department of Orthopedics, Taizhou Municipal Hospital, Taizhou City, Zhejiang, China
Dexamethasone (Dex) causes osteoblast cell injuries. In the present research, we tested the potential effect of SC79, a novel and specific Akt activator, against Dex in osteoblasts. In primary murine osteoblasts and osteoblastic MC3T3-E1 cells, pretreatment with SC79 significantly attenuated Dex-induced cell death. Further, Dex-induced mitochondrial permeability transition pore (mPTP) opening, cytochrome C release and apoptosis activation were dramatically alleviated with SC79 pretreatment in above cells. At the molecular level, SC79 activated Akt, which was indispensable for subsequent osteoblast protection against Dex. Akt inhibitors (LY294002, perifosine and MK-2206) blocked SC79-induced Akt activation and abolished its anti-Dex actions in osteoblasts. Further, SC79 activated Akt downstream Nrf2 (NF-E2-related factor 2) signaling and attenuated Dex-induced oxidative stress in osteoblasts. Nrf2 shRNA knockdown or S40T mutation almost reversed SC79-mediated anti-oxidant and cytoprotective activities in osteoblasts. Together, these results suggest that SC79 activates Akt-Nrf2 signaling to protect osteoblasts from Dex. (C) 2016 Elsevier Inc. All rights reserved.
基金：
The study was supported by the Nature Science Foundation of
China (81171712). Grants from Natural Science Foundation of
Jiangsu Province (BK20151213) and Innovation Project of JiangSu
Province (201423).
第一作者机构：[a]The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China
共同第一作者：
通讯作者：
通讯机构：[*1]The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, San-xiang Road, Suzhou, 215000, China.
推荐引用方式(GB/T 7714)：
Song-tao Li,Nan-nan Chen,Yin-biao Qiao,et al.SC79 rescues osteoblasts from dexamethasone though activating Akt-Nrf2 signaling[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2016,479(1):54-60.doi:10.1016/j.bbrc.2016.09.027.
APA：
Song-tao Li,Nan-nan Chen,Yin-biao Qiao,Wei-li Zhu,Jian-wei Ruan&Xiao-zhong Zhou.(2016).SC79 rescues osteoblasts from dexamethasone though activating Akt-Nrf2 signaling.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,479,(1)
MLA：
Song-tao Li,et al."SC79 rescues osteoblasts from dexamethasone though activating Akt-Nrf2 signaling".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 479..1(2016):54-60
