Insufficient expression of cyclooxygenase-2 protein is associated with retarded degradation of aggregated protein in diabetic glomeruli.
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.
Hirasawa
Yasushi
Y
Department of Pharmacobiology and Therapeutics, Faculty of Pharmacy, Meijo University, Japan. y-hirasawa@nbr.co.jp
Muramatsu
Aiko
A
Suzuki
Yoshio
Y
Nagamatsu
Tadashi
T
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
D052246:Cyclooxygenase 2 Inhibitors; D012333:RNA, Messenger; D012710:Serum Albumin, Bovine; D013311:Streptozocin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone