Involvement of Na⁺/H⁺ exchangers in induction of cyclooxygenase-2 by vacuolar-type (H⁺)-ATPase inhibitors in RAW 264 cells

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• 作者：Fumitaka Kamachi ; Maiko Yanai ; Hyun Seung Ban ; Kenji Ishihara ; JangJa Hong ; Kazuo Ohuchi ; Noriyasu Hirasawa
• 关键词：Vacuolar-type (H⁺)-ATPase ; Na⁺/H⁺ exchanger ; Cyclooxygenase-2 ; RAW 264 cell line
• 刊名：FEBS Letters
• 出版年：2007
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：2 October 2007
• 卷：581
• 期：24
• 页码：4633-4638
• 文件大小：264 K

摘要

In the mouse macrophage-like cell line RAW 264, vacuolar-type (H⁺)-ATPase (V-ATPase) inhibitors, bafilomycin A₁ 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-κB, and by inhibitors of Na⁺/H⁺ exchangers (NHEs). The bafilomycin A₁-induced activation of JNK but not degradation of IκB-α was suppressed by NHE inhibitors and by an inhibitor of Na⁺/Ca²⁺ exchanger SN-6. These results suggested that V-ATPase inhibitors induce the expression of COX-2 via NHE-dependent and -independent pathways.