[Suppression of stress proteins, GRP78, GRP94, calreticulin and calnexin in liver endoplasmic reticulum of rat treated with a highly toxic coplanar PCB].
The present study was addressed on the effect of 3,3',4,4',5-pentachlorobiphenyl (PenCB) to the expression of molecular chaperon proteins, glucose regulated protein (GRP) 78, GRP94, calreticulin and calnexin in liver endoplasmic reticulum of rat by treatment with acute exposure. Male Wistar rats received PenCB in corn oil at once a dose of 10 mg/kg i.p., then at 5 days after treatment the microsomes were prepared. Free-fed and pair-fed control groups were given the vehicle. The microsomal proteins were separated on SDS-PAGE, transferred to membrane and blotted using antibody towards respective chaperone proteins. The protein levels of GRP78, GRP94, calreticulin and calnexin were significantly decreased with the acute exposure. In addition, albumin level in the microsomes was also significantly reduced by the PenCB treatment. The transferrin level was significantly higher than pair-fed but not from free-fed group. These chaperone proteins have important physiological functions against synthesized and/or denatured proteins, which include assembling, folding of proteins. PenCB-treatment may alter the extent of biosynthesis of secretory protein such as albumin through the decreasing levels of chaperone proteins in endoplasmic reticulum. Interestingly, reduced GRP78 protein level by PenCB was not due to decreased mRNA level. Our results suggested that a part of the toxicity of PenCB is associated to significant decrease of the chaperone proteins in the endoplasmic reticulum.
Yoshioka
Y
Y
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582.
Ishii
Y
Y
Ishida
T
T
Yamada
H
H
Oguri
K
K
Motojima
K
K
D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D037281:Calnexin; D037282:Calreticulin; D002352:Carrier Proteins / Q000096:biosynthesis*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006360:Heat-Shock Proteins; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D018832:Molecular Chaperones / Q000096:biosynthesis*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D012261:Ribonucleoproteins / Q000096:biosynthesis*
D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012261:Ribonucleoproteins; C018551:glucose-regulated proteins; D037281:Calnexin; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl