Phenylarsine oxide inhibits heat shock protein 70 induction in cultured guinea pig gastric mucosal cells.
Phenylarsine oxide (PAO) forms a stable ring complex with vicinal dithiols that can be reversed with 2,3-dimercaptopropanol (DMP) but not by dithiothreitol (DTT) or 2-mercaptoethanol (2-ME). PAO at 2 microM or higher inhibited heat shock protein 70 (HSP70) induction within minutes in cultured guinea pig gastric mucosal cells exposed to heat (43 degrees C) for 30 min. PAO did not affect the nuclear translocation and phosphorylation of heat shock factor 1 (HSF1) induced by heat stress, but it completely blocked the binding activity of HSF1 to the heat shock element (HSE), leading to the block of expression of HSP70 mRNA and accumulation of HSP70 in the cells. These inhibitions were completely reversed with 2 microM DMP but not with 0.1 mM DTT or 1 mM 2-ME, suggesting specific interactions between PAO and vicinal dithiol-containing molecules. Thioredoxin (Trx) reversed the inhibition of the binding activity of HSF1 in whole cell extracts prepared from PAO-treated, heat-stressed cells. Our results suggest that PAO may react with vicinal-containing molecules including Trx and specifically block the interaction between HSF1 and HSE.
Rokutan
K
K
Department of Nutrition, School of Medicine, The University of Tokushima, Tokushima 770-8503, Japan. rokutan@nutr.med.tokushims-u.ac.jp
Miyoshi
M
M
Teshima
S
S
Kawai
T
T
Kawahara
T
T
Kishi
K
K
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D004112:Dimercaprol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006168:Guinea Pigs; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D018882:Heat Stress Disorders / Q000378:metabolism; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D013879:Thioredoxins / Q000494:pharmacology; D014157:Transcription Factors; D014443:Tyrosine / Q000378:metabolism
D001152:Arsenicals; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; D004112:Dimercaprol; C029341:oxophenylarsine; D014443:Tyrosine; D013879:Thioredoxins; D008623:Mercaptoethanol