Involvement of Na+/H+ exchangers in induction of cyclooxygenase-2 by vacuolar-type (H+)-ATPase inhibitors in RAW 264 cells.
In the mouse macrophage-like cell line RAW 264, vacuolar-type (H(+))-ATPase (V-ATPase) inhibitors, bafilomycin A(1) and concanamycin A, increased the level of cyclooxygenase (COX)-2 protein and its mRNA. The V-ATPase inhibitor-induced expression of COX-2 was suppressed by inhibitors of c-jun N-terminal kinase (JNK) and nuclear factor-kappaB, and by inhibitors of Na(+)/H(+) exchangers (NHEs). The bafilomycin A(1)-induced activation of JNK but not degradation of IkappaB-alpha was suppressed by NHE inhibitors and by an inhibitor of Na(+)/Ca(2+) exchanger SN-6. These results suggested that V-ATPase inhibitors induce the expression of COX-2 via NHE-dependent and -independent pathways.
Kamachi
Fumitaka
F
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Yanai
Maiko
M
Ban
Hyun Seung
HS
Ishihara
Kenji
K
Hong
Jangja
J
Ohuchi
Kazuo
K
Hirasawa
Noriyasu
N
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053778:Thiazolidines / Q000494:pharmacology; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism