Modulation of subcellular particles of the rat small intestine and liver by ebselen.
Reactions between ebselen and subcellular particles of rat liver were investigated by monitoring the activity of mitochondrial glutamate dehydrogenase and microsomal glucose 6-phosphate dehydrogenase. Rat small intestine lactate dehydrogenase was purified and was also used in the reaction between cytosolic protein and ebselen. Glutamate dehydrogenase in intact rat liver mitochondria was completely resistant to ebselen, but the enzyme was significantly inactivated in broken mitochondria mediated by Triton X-100, reflecting the fact that ebselen was not transported through the mitochondrial membrane into the matrix. Glucose 6-phosphate dehydrogenase in rat liver microsomes was inactivated by ebselen, accompanied by a slight decrease in the thiol groups of microsomal membrane protein. Purified cytosolic lactate dehydrogenase was inactivated concentration- and time-dependent by ebselen. The activity of rat small intestine lactate dehydrogenase abolished by ebselen was significantly restored by incubation with purified rat small intestine thioltransferase in the presence of reduced glutathione (GSH). The level of thiol groups in rat liver microsome membrane protein decreased by ebselen was partially restored by an incubation with purified rat liver thioltransferase in the presence of GSH. The results suggested that thioltransferase can cleave the Se-S conjugates between ebselen and cytosolic proteins or microsomal membrane proteins in the presence of GSH.
Mizoguchi
T
T
Laboratory of Bio-Functional Engineering, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Nishinaka
T
T
Nanjo
H
H
Yagi
K
K
Hakusui
H
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D054833:Isoindoles; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D011506:Proteins; D013438:Sulfhydryl Compounds; C042986:ebselen; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D015238:Sulfotransferases