The protective effect of a newly developed molecular chaperone-inducer against mouse ischemic acute kidney injury.
Activation of the unfolded protein response (UPR) has been suggested to attenuate renal ischemia-reperfusion (I/R) injury. We recently found a compound, namely BIX, that activated the UPR selectively through the activating transcription factor 6 pathway. This study examined the effect of BIX on renal I/R injury in mice. BIX selectively up-regulated renal BiP mRNA and protein. Pretreatment with BIX significantly ameliorated renal I/R injury. Co-administration of BIX and tunicamycin, a non-selective UPR inducer, provided no additional protection. Our results suggest that the UPR activation by BIX leads to a novel drug therapy against renal I/R injury.
Prachasilchai
Worapat
W
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Japan.
Sonoda
Hiroko
H
Yokota-Ikeda
Naoko
N
Ito
Katsuaki
K
Kudo
Takashi
T
Imaizumi
Kazunori
K
Ikeda
Masahiro
M
D000818:Animals; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy*; D007668:Kidney / Q000293:injuries; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D013861:Thiocyanates / Q000627:therapeutic use*; D015533:Transcriptional Activation; D014415:Tunicamycin / Q000008:administration & dosage / Q000494:pharmacology; D015854:Up-Regulation
C527742:1-(3,4-dihydroxyphenyl)-2-thiocyanate-ethanone; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D013861:Thiocyanates; D014415:Tunicamycin