Bone marrow-derived mesenchymal stem cells prevent the apoptosis of neuron-like PC12 cells via erythropoietin expression.
It is known that bone marrow-derived mesenchymal stem cells (BM-MSCs) are able to improve neuronal function through secretion of trophic factors in animal models of middle cerebral artery occlusion (MCAo). In this study, we demonstrated that incubation of BM-MSCs protects PC12 cells against apoptosis induced by CoCl(2) via the production of erythropoietin (EPO). Addition of CoCl(2) to BM-MSCs cultures induced the expression of EPO in a time-dependent manner. Additionally, BM-MSCs co-culture protected PC12 cells against apoptosis induced by CoCl(2) in a ratio-dependent manner. To explore whether expression of EPO induced by CoCl(2) is required for BM-MSCs-mediated cytoprotection, we transfected BM-MSCs with EPO small interfering RNA (siRNA). Knocking-down EPO abrogated increases in EPO expression induced by CoCl(2), and the cytoprotective effect of BM-MSCs. Reverse transcriptase polymerase chain reaction results showed that EPO siRNA reversed upregulation of Bcl-2, Bcl-X(L) expression and downregulation of Bax, Bak, caspase-9, and caspase-3 expression. Our results revealed that the protective effect of BM-MSCs against PC12 cell apoptosis induced by CoCl(2) might be dependent on EPO expression, at least in part, via the regulation of Bcl-2 family members and caspases.
Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China.
Shi-Jing
SJ
Mo
Qian
Q
Zhong
Yan-Fang
YF
Zhou
David B
DB
Deng
Xiu-Quan
XQ
Zhang
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D019610:Cytoprotection; D004921:Erythropoietin / Q000096:biosynthesis* / Q000235:genetics; D055785:Gene Knockdown Techniques; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D004921:Erythropoietin; D003035:Cobalt; D020169:Caspases; C018021:cobaltous chloride