Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells.
In recent years, the understanding that regeneration progresses at the level of the myocardium has placed stem cell research at the center stage in cardiology. Despite an increasing interest in cell transplant research, relatively little is known about the biochemical regulation of the stem cell itself after transplantation into an ischemic heart. We demonstrated here, using rat mesenchymal stem cells (MSCs), that cells undergo caspase-dependent apoptosis in response to hypoxia and serum deprivation (SD), which are both components of ischemia in vivo. In particular, the treated cells exhibited mitochondrial dysfunction, including cytochrome C release, loss in DeltaPsim, and Bax accumulation, but in a p53-independent manner. Although the cells treated by hypoxia/SD possess the activity of caspase-8, zIEDT-fmk, a specific caspase-8 inhibitor, failed to inhibit cell apoptosis induced in our system. Taken together, our findings indicate that MSCs are sensitive to hypoxia/SD stimuli that involve changes in mitochondrial integrity and function but are potentially independent of caspase-8.
Zhu
Weiquan
W
Research Center for Cardiovascular Regenerative Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, People's Republic of China.
Chen
Jinghai
J
Cong
Xiangfeng
X
Hu
Shengshou
S
Chen
Xi
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D016895:Culture Media, Serum-Free; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D051381:Rats; D014178:Translocation, Genetic; D051028:bcl-2-Associated X Protein / Q000235:genetics
D016895:Culture Media, Serum-Free; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases