title: High sensitivity of embryonic stem cells to proteasome inhibitors correlates with low expression of heat shock protein and decrease of pluripotent cell marker expression.
abstract: The ubiquitin-proteasome system is a major proteolytic system for nonlysosomal degradation of cellular proteins. Here, we investigated the response of mouse embryonic stem (ES) cells under proteotoxic stress. Proteasome inhibitors induced expression of heat shock protein 70 (HSP70) in a concentration- and time-dependent manner, and also induced apoptosis of ES cells. Importantly, more apoptotic cells were observed in ES cells compared with other somatic cells. To understand this phenomenon, we further investigated the expression of HSP70 and pluripotent cell markers. HSP70 expression was more significantly increased in somatic cells than in ES cells, and expression levels of pluripotent cell markers such as Oct4 and Nanog were decreased in ES cells. These results suggest that higher sensitivity of ES cells to proteotoxic stress may be related with lower capacity of HSP70 expression and decreased pluripotent cell marker expression, which is essential for the survival of ES cells.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 361-763, Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Park
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Kim
authors.forename: Yang-Hwa
authors.initials: YH
authors.lastname: Ha
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism; D061988:Proteasome Inhibitors
chemical_list: D015415:Biomarkers; D015853:Cysteine Proteinase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D007976:Leupeptins; D009842:Oligopeptides; D061988:Proteasome Inhibitors; C067713:lactacystin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine; C078846:epoxomicin