MEK/ERK pathway mediates cytoprotection of salvianolic acid B against oxidative stress-induced apoptosis in rat bone marrow stem cells.
To improve the survival and/or differentiation of grafted BMSCs (bone marrow stem cells) represents one of the challenges for the promising cell-based therapy. Considerable reports have implicated Sal B (salvianolic acid B), a potent aqueous extract of Salvia miltiorrhiza, in enhancing the survival of cells under various conditions. In this study, we investigated the effect of Sal B on H₂O₂-induced apoptosis in rat BMSCs, focusing on the survival signalling pathways. Results indicated that the MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] inhibitor (PD98059) and 10 μM Sal B remarkably prevented BMSCs from H₂O₂-induced apoptosis through attenuating caspase-3 activation, which is accompanied by the significant up-regulation of Bcl-2. In addition, the ROS (reactive oxygen species) accumulation was also reduced after Sal B treatment. Furthermore, Sal B inhibited the ERK1/2 phosphorylations stimulated by H₂O₂. Taken together, our results showed that H₂O₂-induced apoptosis in BMSCs via the ROS/MEK/ERK1/2 pathway and Sal B may exert its cytoprotection through mediating the pathway.
Lu
Biyan
B
Department of Pathophysiology, Sun YatSen University, Guangzhou, Peoples Republic of China.
Ye
Zhizhong
Z
Deng
Yubin
Y
Wu
Hongfu
H
Feng
Jianqiang
J
D000818:Animals; D017209:Apoptosis; D001572:Benzofurans / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019610:Cytoprotection; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D053630:Depsides
D001572:Benzofurans; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D020929:Mitogen-Activated Protein Kinase Kinases; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; C076944:salvianolic acid B; D053630:Depsides; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one