RRC ID 73743
著者 Matsuo K, Abiko Y, Yamano S, Matsusue K, Kumagai Y.
タイトル Activation of HSP90/HSF1 Signaling as an Adaptive Response to an Electrophilic Metabolite of Morphine.
ジャーナル Biol Pharm Bull
Abstract Morphinone (MO) is an electrophilic metabolite of morphine that covalently binds to protein thiols, resulting in toxicity in vitro and in vivo. We have previously identified a variety of redox signaling pathways that are activated during electrophilic stress. However, the role of MO in such activation remains unknown. In this study, we examined whether MO could activate heat shock protein (HSP) 90/heat shock factor (HSF) 1 signaling in HepG2 cells. MO exposure caused S-modification of HSP90 (determined using biotin-PEAC5-maleimide labeling) and nuclear translocation of transcription factor HSF1, thereby up-regulating its downstream genes encoding B-cell lymphoma 2-associated anthanogene 3 and heat shock 70 kDa protein 1. However, dihydromorphinone, a non-electrophilic metabolite of morphine, had little effect on HSF1 activation or upregulation of these genes, suggesting that covalent modification plays a role in this process and that the HSP90/HSF1 pathway is a redox-signaled adaptive response to morphine metabolism.
巻・号 46(2)
ページ 334-337
公開日 2023-1-1
DOI 10.1248/bpb.b22-00531
PMID 36724961
MeSH DNA-Binding Proteins* / genetics DNA-Binding Proteins* / metabolism HSP70 Heat-Shock Proteins / genetics HSP90 Heat-Shock Proteins Heat Shock Transcription Factors / genetics Hep G2 Cells Humans Morphine* / pharmacology Transcription Factors / genetics Transcription Factors / metabolism
IF 1.863
リソース情報
ヒト・動物細胞 Hep G2(RCB1886)