Induction of cyclooxygenase-2 expression in glomeruli by aggregated protein.
Cyclooxygenase has two isozymes, a constitutive type (cyclooxygenase-1) and an inducible type (cyclooxygenase-2). The aim of the present study was to determine whether cyclooxygenase-2 is associated with the increased production in prostaglandin E2 in glomeruli by aggregated protein. Mice were injected with aggregated bovine serum albumin. Glomeruli were isolated using sieves and a magnet. Production of prostaglandin E2 was increased in glomeruli after injection of aggregated bovine serum albumin. RT-PCR analysis indicated enhanced expression of cyclooxygenase-2 mRNA in aggregated bovine serum albumin-loaded glomeruli. Western blotting analysis indicated an increase in cyclooxygenase-2 protein in glomeruli by aggregated bovine serum albumin. Glomeruli were incubated with indomethacin, NS-398 or niflumic acid in the presence of arachidonic acid. Indomethacin resulted in remarkable reduction of prostaglandin E2 levels in aggregated bovine serum albumin-loaded glomeruli. Niflumic acid also inhibited prostaglandin E2 production, and its inhibitory rate was more than that of NS-398. In conclusion, aggregated protein induces cyclooxygenase-2 in glomeruli, suggesting that cyclooxygenase-2 is involved in the process of disposal of aggregated protein in glomeuli.
Nagamatsu
Tadashi
T
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan. nagamts@ccmfs.meijo-u.ac.jp
Ishikami
Hitomi
H
Nishiyama
Tsutomu
T
Suzuki
Yoshio
Y
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007527:Isoenzymes / Q000096:biosynthesis*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D012710:Serum Albumin, Bovine; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases