title: HMBOX1 interacts with MT2A to regulate autophagy and apoptosis in vascular endothelial cells.
abstract: We previously found that Homeobox containing 1 (HMBOX1) was required for bone mesenchymal stem cell (BMSC) and mouse embryonic stem cell (ESC) differentiation into vascular endothelial cells (VECs). However, the function of HMBOX1 in VECs is still unknown. In this study, we found that HMBOX1 was abundantly expressed in the cytoplasm of human umbilical vascular endothelial cells (HUVECs). Knockdown of HMBOX1 induced apoptosis and inhibited autophagy. Overexpression of HMBOX1 inhibited apoptosis induced by fibroblast growth factor 2 deprivation and promoted autophagy. Metallothionein 2A (MT2A) was identified as an interaction protein with HMBOX1 by yeast two-hybrid assay, and confirmed by co-immunoprecipitation. Overexpression of HMBOX1 elevated intracellular free zinc level. Knockdown of MT2A inhibited this phenomenon. Moreover, N,N,N = ,N = -tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, reversed the anti-apoptosis and pro-autophagy effects of HMBOX1. In conclusion, HMBOX1 regulated intracellular free zinc level by interacting with MT2A to inhibit apoptosis and promote autophagy in VECs.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: HanLin
authors.initials: H
authors.lastname: Ma
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Le
authors.initials: L
authors.lastname: Su
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: HongWei
authors.initials: H
authors.lastname: Yue
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: XiaoLei
authors.initials: X
authors.lastname: Yin
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: ShangLi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.|Institute of Pathology and Southwest Cancer Center, Third Military Medical University, Chongqing, 400038, China.
authors.forename: HsiangFu
authors.initials: H
authors.lastname: Kung
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: ZhiGang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.|The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, 250012, China.
authors.forename: JunYing
authors.initials: J
authors.lastname: Miao
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D005021:Ethylamines / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008668:Metallothionein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D015032:Zinc / Q000378:metabolism*
chemical_list: D005021:Ethylamines; C512050:HMBOX1 protein, human; D018398:Homeodomain Proteins; C491053:MT2A protein, human; C511824:N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine; D011725:Pyridines; D034741:RNA, Small Interfering; D016222:Fibroblast Growth Factor 2; D008668:Metallothionein; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D015032:Zinc