Effect of pranoprofen on endoplasmic reticulum stress in the primary cultured glial cells.
Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of CNS diseases such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia. In the present study, we investigated the effect of pranoprofen, a non-steroidal anti-inflammatory drug (NSAID), on endoplasmic reticulum stress responses in the primary cultured glial cells. Pranoprofen inhibited ER stress-induced glucose regulated protein 78 (GRP78) expression, an ER-localized molecular chaperon. Moreover, pranoprofen inhibited ER stress-induced CCAAT/enhancer-binding protein homologous protein (CHOP) expression, an apoptotic transcription factor. ER stress-induced phosphorylation of alpha-subunit of eukaryotic initiation factor-2 (eIF2alpha) has been reported to be involved in CHOP induction. Interestingly, pranoprofen alone induced eIF2alpha phosphorylation, which was further increased by ER stress. On the other hand, ER stress-induced X-box-binding protein 1 (XBP-1) splicing was inhibited in pranoprofen-treated cells. Thus, the inhibitory effect of pranoprofen on ER stress-related genes (GRP78 and CHOP) would be mediated through the inhibition of XBP-1 splicing. In the present study, pranoprofen has been suggested to affect ER stress. The present results may have important implications for understanding ER 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.
Sasaki
Miyako
M
Baba
Sachiko
S
Ozawa
Koichiro
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011422:Propionates / Q000494:pharmacology*; D012313:RNA / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D051742:Transcription Factor CHOP / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D018076:DNA, Complementary; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D011422:Propionates; D051742:Transcription Factor CHOP; C043940:pyranoprofen; D012313:RNA