RRC ID 45217
著者 Miura Y, Sato T, Sakurai Y, Sakai R, Hiraoka W, Endo T.
タイトル Hyper-O-GlcNAcylation inhibits the induction of heat shock protein 70 (Hsp 70) by sodium arsenite in HeLa cells.
ジャーナル Biol Pharm Bull
Abstract O-Linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins that is responsive to cellular stress. However, the role of O-GlcNAcylation in the induction of heat shock proteins (Hsps) by arsenite remains unclear. We used O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of O-GlcNAcase, and glucosamine (GlcN), an enhancer of the hexosamine biosynthesis pathway, or O-GlcNAc transferase (OGT) short interfering RNA (siRNA) to enhance or suppress cellular O-GlcNAcylation levels, respectively, in HeLa cells. The exposure to arsenite increased O-GlcNAcylation and Hsp 70 levels in HeLa cells. However, the pre-treatment with PUGNAc or GlcN, which enhanced O-GlcNAcylation levels, decreased the arsenite-induced expression of Hsp 70. The pre-treatment with OGT siRNA, which suppressed O-GlcNAcylation levels, did not affect the induction of Hsp 70. We then examined the effects of O-GlcNAcylation on the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1), and found that neither the nuclear translocation nor phosphorylation of HSF1 was regulated by O-GlcNAcylation. Finally, Hsp 70 mRNA expression was induced by arsenite, whereas the addition of PUGNAc slightly suppressed its induction. These results indicate that O-GlcNAcylation is related to arsenite-induced Hsp 70 expression, and demonstrated that hyper-O-GlcNAcylation inhibited the induction of Hsp 70 via transcriptional factors instead of HSF1.
巻・号 37(8)
ページ 1308-14
公開日 2014-1-1
DOI 10.1248/bpb.b14-00170
PII DN/JST.JSTAGE/bpb/b14-00170
PMID 25087952
MeSH Acetylglucosamine / analogs & derivatives Acetylglucosamine / pharmacology Acylation Arsenites / toxicity* DNA-Binding Proteins / metabolism Glucosamine / pharmacology HSP70 Heat-Shock Proteins / genetics HSP70 Heat-Shock Proteins / metabolism* HeLa Cells Heat Shock Transcription Factors Humans N-Acetylglucosaminyltransferases / antagonists & inhibitors N-Acetylglucosaminyltransferases / genetics N-Acetylglucosaminyltransferases / metabolism* Oxidative Stress / drug effects Oximes / pharmacology Phenylcarbamates / pharmacology Protein Processing, Post-Translational RNA, Messenger / metabolism RNA, Small Interfering / genetics Sodium Compounds / toxicity* Transcription Factors / metabolism
IF 1.863
引用数 0
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 HeLa(RCB0007)