title: Insufficient expression of cyclooxygenase-2 protein is associated with retarded degradation of aggregated protein in diabetic glomeruli.
abstract: To elucidate the involvement of cyclooxygenase (COX) in degradation of aggregated protein in diabetic glomeruli, we used streptozotocin (STZ)-induced diabetic mice and aggregated bovine serum albumin (a-BSA) as a model protein. There was a higher deposition of a-BSA in diabetic glomeruli compared to normal glomeruli 18 h after a-BSA injection at 4 and 8 weeks after STZ. Degradation of a-BSA was confirmed using isolated glomeruli. Diabetic glomeruli produced prostaglandin E(2) (PGE(2)) more than normal glomeruli in the basal level at 8 weeks. a-BSA caused further increase of PGE(2) production in normal glomeruli, but not in diabetic glomeruli. Niflimic acid, a selective COX-2 inhibitor, reduced PGE(2) production of normal glomeruli in the a-BSA loading group, but not that in the control group. In diabetic glomeruli, niflimic acid reduced PGE(2) production in both the control group and a-BSA loading group. In normal glomeruli, a-BSA increased expressions of both COX-2 mRNA and protein. However, in diabetic glomeruli, a-BSA increased COX-2 mRNA expression but not COX-2 protein expression. These results suggest that retarded degradation of aggregated protein in diabetic glomeruli is associated with lack of further expression of COX-2 protein and further production of PGE(2) in response to aggregated protein.
authors.affiliation: Department of Pharmacobiology and Therapeutics, Faculty of Pharmacy, Meijo University, Japan. y-hirasawa@nbr.co.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirasawa
authors.forename: Aiko
authors.initials: A
authors.lastname: Muramatsu
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagamatsu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology*; D003928:Diabetic Nephropathies / Q000201:enzymology*; D015232:Dinoprostone / Q000378:metabolism; D007678:Kidney Glomerulus / Q000201:enzymology*; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013311:Streptozocin
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D012333:RNA, Messenger; D012710:Serum Albumin, Bovine; D013311:Streptozocin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone