Inhibitory effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride, a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression.
Endoplasmic reticulum stress contributes to several diseases such as neurodegenerative disorders and diabetes. In the previous report, we found that phosphatidylinositol 3-kinase (PI3K) down-regulation is important for inducing CHOP expression, an endoplasmic reticulum stress-induced transcription factor. In the present study, we investigated the effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor, on PI3K inhibitor-induced CHOP expression. We found that AEBSF completely inhibited PI3K inhibitor-induced CHOP expression at both mRNA and protein levels. It is suggested that AEBSF is an important drug from a pharmacological point of view and the results may have important implications for understanding endoplasmic reticulum stress-related diseases.
Hosoi
Toru
T
Department of Pharmacotherapy Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Hyoda
Kanae
K
Okuma
Yasunobu
Y
Nomura
Yasuyuki
Y
Ozawa
Koichiro
K
D000818:Animals; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics*
D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D013450:Sulfones; D051742:Transcription Factor CHOP; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D012697:Serine Endopeptidases