title: ER stress response during the differentiation of H9 cells induced by retinoic acid.
abstract: Endoplasmic reticulum (ER) stress occurs during early embryonic development. The aim of this study is to determine whether ER stress occurs during human embryonic stem cell differentiation induced by retinoic acid (RA). H9 human embryonic stem cells were subjected to RA treatment for up to 29days to induce differentiation. HEK293 cells were treated with RA as a control. The results demonstrate that several ER stress-responsive genes are differentially regulated in H9 and HEK293 cells in response to 5days of RA treatment. GRP78/Bip was upregulated in H9 cells but downregulated in HEK293 cells. eIF2α was downregulated in H9 cells but not in HEK293 cells. Phosphorylation of eIF2α was downregulated in H9 cells but upregulated in HEK293 cells. XBP-1 was downregulated immediately after RA treatment in H9 cells, but its downregulation was much slower in HEK293 cells. Additionally, two ER-resident E3 ubiquitin ligases, gp78 and Hrd1, were both upregulated in H9 cells following 5 days of exposure to RA. Moreover, the protein Bcl2 was undetectable in H9 cells and H9-derived cells but was expressed in HEK293 cells, and it expression in the two types of cells was unaltered by RA treatment. In H9 cells treated with RA for 29 days, GRP78/Bip, XBP-1 and Bcl2 were all upregulated. These results suggest that ER stress is involved in H9 cell differentiation induced by RA.
authors.affiliation: Clinical Pharmacology Institute, Anhui Medical University, Hefei, Anhui 230032, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Yongwang
authors.initials: Y
authors.lastname: Zhong
authors.forename: Andria
authors.initials: A
authors.lastname: Apostolou
authors.forename: Shengyun
authors.initials: S
authors.lastname: Fang
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation; D060285:Receptors, Autocrine Motility Factor / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; C000717247:HSPA5 protein, human; D014212:Tretinoin; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor; C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases