PMID- 28112581 OWN - NLM STAT- MEDLINE DCOM- 20170619 LR - 20211204 IS - 1551-4005 (Electronic) IS - 1538-4101 (Print) IS - 1551-4005 (Linking) VI - 16 IP - 5 DP - 2017 Mar 4 TI - Toxoplasma gondii induces autophagy and apoptosis in human umbilical cord mesenchymal stem cells via downregulation of Mcl-1. PG - 477-486 LID - 10.1080/15384101.2017.1281484 [doi] AB - Autophagy and apoptosis are critical for controlling Toxoplasma gondii (T. gondii) infection. T. gondii infection during pregnancy can damage the fetus and cause birth defects; however, the molecular mechanisms of this process are poorly understood. This study aims to determine the activities of autophagy and apoptosis as well as their regulatory mechanisms during T. gondii infection by using human umbilical cord mesenchymal stem cells (hUC-MSCs) as a model of congenital diseases. LC3B, a hallmark protein of autophagy was incrementally upregulated with the infection duration, whereas p62 was downregulated in T. gondii-infected hUC-MSCs. Concurrent to this result, the invasion of T. gondii into hUC-MSCs increased in a time-dependent manner. The expression levels of Bcl-2 family proteins including Bcl-2, Bcl-xL, Bim, Bax, Bid and Bak were not altered; however, Mcl-1 levels in hUC-MSCs were dramatically decreased upon T. gondii infection. In addition, at 24 h post-infection, cleaved PARP and cleaved caspase-3 protein levels were elevated in hUC-MSCs. Importantly, Mcl-1 overexpression reduced the levels of autophagy- and apoptosis-related proteins in T. gondii-infected hUC-MSCs. Mcl-1 proteins were primarily expressed in the fraction containing mitochondria and strongly interacted with Beclin-1 under normal conditions; however, these interactions were remarkably attenuated by T. gondii infection. These results suggest that mitochondrial Mcl-1 is an essential signaling mediator regulating the activation of autophagy and apoptosis during T. gondii infection. FAU - Chu, Jia-Qi AU - Chu JQ AD - a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. AD - b Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Jing, Kai-Peng AU - Jing KP AD - a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Gao, Xiang AU - Gao X AD - a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Li, Peng AU - Li P AD - a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Huang, Rui AU - Huang R AD - a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Niu, Yan-Ru AU - Niu YR AD - b Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Yan, Shou-Quan AU - Yan SQ AD - a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Kong, Jun-Chao AU - Kong JC AD - b Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Yu, Cai-Yuan AU - Yu CY AD - c Department of Gastroenterology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Shi, Ge AU - Shi G AD - d Department of Dermatology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Fan, Yi-Ming AU - Fan YM AD - d Department of Dermatology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Lee, Young-Ha AU - Lee YH AD - e Department of Infection Biology , Chungnam National University School of Medicine , Daejeon , Korea. FAU - Zhou, Yu AU - Zhou Y AD - c Department of Gastroenterology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. FAU - Quan, Juan-Hua AU - Quan JH AD - c Department of Gastroenterology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China. LA - eng PT - Journal Article DEP - 20170123 PL - United States TA - Cell Cycle JT - Cell cycle (Georgetown, Tex.) JID - 101137841 RN - 0 (BECN1 protein, human) RN - 0 (Beclin-1) RN - 0 (Myeloid Cell Leukemia Sequence 1 Protein) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - *Apoptosis MH - *Autophagy MH - Beclin-1 MH - Cell Survival MH - *Down-Regulation MH - Humans MH - Mesenchymal Stem Cells/*cytology/*metabolism MH - Mitochondria/metabolism MH - Models, Biological MH - Myeloid Cell Leukemia Sequence 1 Protein/*metabolism MH - Protein Binding MH - TOR Serine-Threonine Kinases/metabolism MH - Toxoplasma/*physiology MH - Umbilical Cord/*cytology PMC - PMC5351927 OTO - NOTNLM OT - Beclin-1 OT - Mcl-1 OT - Toxoplasma gondii OT - apoptosis OT - autophagy OT - cell death OT - umbilical cord mesenchymal stem cell EDAT- 2017/01/24 06:00 MHDA- 2017/06/20 06:00 PMCR- 2018/01/23 CRDT- 2017/01/24 06:00 PHST- 2017/01/24 06:00 [pubmed] PHST- 2017/06/20 06:00 [medline] PHST- 2017/01/24 06:00 [entrez] PHST- 2018/01/23 00:00 [pmc-release] AID - 1281484 [pii] AID - 10.1080/15384101.2017.1281484 [doi] PST - ppublish SO - Cell Cycle. 2017 Mar 4;16(5):477-486. doi: 10.1080/15384101.2017.1281484. Epub 2017 Jan 23.