| RRC ID |
58453
|
| 著者 |
Nakata T, Hirano Y, Katsumata H, Tokita R, Yagi T, Toyoshima Y, Minami S.
|
| タイトル |
Growth hormone activates X-box binding protein 1 in a sexually dimorphic manner through the extracellular signal-regulated protein kinase and CCAAT/enhancer-binding protein β pathway in rat liver.
|
| ジャーナル |
Endocr J
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| Abstract |
Growth hormone (GH) has multiple physiological roles, acting on many organs. In order to investigate its roles in rat liver, we tried to identify novel genes whose transcription was regulated by GH. We identified X-box binding protein 1 (Xbp1) as a candidate gene. XBP1 is a key transcription factor activated in response to endoplasmic reticulum (ER) stress. The purpose of this study was to investigate the mode of action of GH on XBP1, including the relation with ER stress, sex-dependent expression of the mRNA, and the signaling pathway. Intravenous administration of GH rapidly and transiently increased Xbp1 mRNA in hypophysectomized rat livers. Neither phosphorylated inositol-requiring-1α (IRE1α) nor phosphorylated PKR-like ER kinase (PERK) increased, suggesting that Xbp1 expression is induced by an ER stress-independent mechanism. The active form of XBP1(S) protein was increased by GH administration and was followed by an increased ER-associated dnaJ protein 4 (ERdj4) mRNA level. XBP1(S) protein levels were predominantly identified in male rat livers with variations among individuals similar to those of phosphorylated signal transducer and activator of transcription 5B (STAT5B), suggesting that XBP1(S) protein levels are regulated by the sex-dependent secretary pattern of GH. The GH signaling pathway to induce Xbp1 mRNA was examined in rat hepatoma H4IIE cells. GH induced the phosphorylation of CCAAT/enhancer-binding protein β (C/EBPβ) following extracellular signal-regulated protein kinase (ERK) phosphorylation. Taken together, the results indicated that XBP1 is activated by GH in rat liver in a sexually dimorphic manner via ERK and C/EBPβ pathway.
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| 巻・号 |
67(2)
|
| ページ |
185-200
|
| 公開日 |
2020-2-28
|
| DOI |
10.1507/endocrj.EJ19-0240
|
| PMID |
31748431
|
| MeSH |
Animals
CCAAT-Enhancer-Binding Protein-beta / metabolism*
Cell Line, Tumor
Endoplasmic Reticulum Stress / genetics
Endoribonucleases / drug effects
Endoribonucleases / metabolism
Growth Hormone / pharmacology*
HSP40 Heat-Shock Proteins / drug effects
HSP40 Heat-Shock Proteins / genetics
Hypophysectomy
Liver / drug effects*
Liver / metabolism
MAP Kinase Signaling System*
Multienzyme Complexes / drug effects
Multienzyme Complexes / metabolism
Protein Serine-Threonine Kinases / drug effects
Protein Serine-Threonine Kinases / metabolism
RNA, Messenger / drug effects*
RNA, Messenger / metabolism
Rats
STAT5 Transcription Factor / drug effects
STAT5 Transcription Factor / metabolism
Sex Characteristics
Signal Transduction
X-Box Binding Protein 1 / drug effects*
X-Box Binding Protein 1 / genetics
eIF-2 Kinase / drug effects
eIF-2 Kinase / metabolism
|
| IF |
1.952
|
| 引用数 |
1
|
| リソース情報 |
| 遺伝子材料 |
rat LAP* (RDB17915)
rat active STAT5B (RDB17922)
rat LAP*T189A (RDB17933)
rat Xbp1-Luc (RDB17934) |
