PMID- 26985709
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20210927
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Linking)
VI  - 25
IP  - 10
DP  - 2016 May 15
TI  - Autophagy Plays a Protective Role in Tumor Necrosis Factor-alpha-Induced Apoptosis of 
      Bone Marrow-Derived Mesenchymal Stem Cells.
PG  - 788-97
LID - 10.1089/scd.2015.0387 [doi]
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) are being broadly investigated 
      for treating numerous inflammatory diseases. However, the low survival rate of 
      BMSCs during the transplantation process has limited their application. Autophagy 
      can maintain cellular homeostasis and protect cells against environmental 
      stresses. Tumor necrosis factor-alpha (TNF-alpha) is an important inflammatory cytokine 
      that can induce both autophagy and apoptosis of BMSCs. However, the actual role 
      of autophagy in TNF-alpha-induced apoptosis of BMSCs remains poorly understood. In 
      the current study, BMSCs were treated with TNF-alpha/cycloheximide (CHX), and cell 
      death was examined by the Cell Counting Kit-8, Hoechst 33342 staining, and flow 
      cytometric analysis as well as by the level of caspase-3 and caspase-8. 
      Meanwhile, autophagic flux was examined by analyzing the level of 
      microtubule-associated protein light chain 3 B (LC3B)-II and SQSTEM1/p62 and by 
      examining the amount of green fluorescent protein-LC3B by fluorescence 
      microscopy. Then, the cell death and autophagic flux of BMSCs were examined after 
      pretreatment and cotreatment with 3-methyladenine (3-MA, autophagy inhibitor) or 
      rapamycin (Rap, autophagy activator) together with TNF-alpha/CHX. Moreover, BMSCs 
      pretreated with lentiviruses encoding short hairpin RNA of beclin-1 (BECN1) were 
      treated with TNF-alpha/CHX, and then cell death and autophagic flux were detected. We 
      showed that BMSCs treated with TNF-alpha/CHX presented dramatically elevated 
      autophagic flux and cell death. Furthermore, we showed that 3-MA and shBECN1 
      treatment accelerated TNF-alpha/CHX-induced apoptosis, but that Rap treatment 
      ameliorated cell death. Our results demonstrate that autophagy protects BMSCs 
      against TNF-alpha-induced apoptosis. Enhancing the autophagy of BMSCs may elevate 
      cellular survival in an inflammatory microenvironment.
FAU - Yang, Rui
AU  - Yang R
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Ouyang, Yi
AU  - Ouyang Y
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Li, Weiping
AU  - Li W
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Wang, Peng
AU  - Wang P
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Deng, Haiquan
AU  - Deng H
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Song, Bin
AU  - Song B
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Hou, Jingyi
AU  - Hou J
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Chen, Zhong
AU  - Chen Z
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Xie, Zhongyu
AU  - Xie Z
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Liu, Zhenhua
AU  - Liu Z
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Li, Jinteng
AU  - Li J
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Cen, Shuizhong
AU  - Cen S
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Wu, Yanfeng
AU  - Wu Y
AD  - 2 Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University , 
      Guangzhou, People's Republic of China .
FAU - Shen, Huiyong
AU  - Shen H
AD  - 1 Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
LA  - eng
PT  - Journal Article
DEP - 20160420
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Beclin-1)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 5142-23-4 (3-methyladenine)
RN  - 98600C0908 (Cycloheximide)
RN  - JAC85A2161 (Adenine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Adult
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Beclin-1/metabolism
MH  - Bone Marrow Cells/*cytology/drug effects/metabolism
MH  - Cell Differentiation/drug effects
MH  - Cycloheximide/pharmacology
MH  - Female
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - Multipotent Stem Cells/cytology/drug effects
MH  - Phenotype
MH  - RNA, Small Interfering/metabolism
MH  - Sirolimus/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2016/03/18 06:00
MHDA- 2017/08/02 06:00
CRDT- 2016/03/18 06:00
PHST- 2016/03/18 06:00 [entrez]
PHST- 2016/03/18 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
AID - 10.1089/scd.2015.0387 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2016 May 15;25(10):788-97. doi: 10.1089/scd.2015.0387. Epub 2016 
      Apr 20.