title: Toxoplasma gondii induces autophagy and apoptosis in human umbilical cord mesenchymal stem cells via downregulation of Mcl-1.
abstract: 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.
authors.affiliation: a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.|b Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Chu
authors.affiliation: a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Kai-Peng
authors.initials: KP
authors.lastname: Jing
authors.affiliation: a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: b Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Niu
authors.affiliation: a Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Shou-Quan
authors.initials: SQ
authors.lastname: Yan
authors.affiliation: b Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Jun-Chao
authors.initials: JC
authors.lastname: Kong
authors.affiliation: c Department of Gastroenterology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Cai-Yuan
authors.initials: CY
authors.lastname: Yu
authors.affiliation: d Department of Dermatology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Ge
authors.initials: G
authors.lastname: Shi
authors.affiliation: d Department of Dermatology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Fan
authors.affiliation: e Department of Infection Biology , Chungnam National University School of Medicine , Daejeon , Korea.
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Lee
authors.affiliation: c Department of Gastroenterology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: c Department of Gastroenterology , Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
authors.forename: Juan-Hua
authors.initials: JH
authors.lastname: Quan
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D000071186:Beclin-1; D002470:Cell Survival; D015536:Down-Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D011485:Protein Binding; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014122:Toxoplasma / Q000502:physiology*; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: C491997:BECN1 protein, human; D000071186:Beclin-1; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D058570:TOR Serine-Threonine Kinases
keywords: Beclin-1; Mcl−1; Toxoplasma gondii; apoptosis; autophagy; cell death; umbilical cord mesenchymal stem cell