Kamachi Fumitaka, Yanai Maiko, Ban Hyun Seung, Ishihara Kenji, Hong Jangja, Ohuchi Kazuo, Hirasawa Noriyasu
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
FEBS Lett. 2007 Oct 2;581(24):4633-8. doi: 10.1016/j.febslet.2007.08.055. Epub 2007 Sep 7.
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.
在小鼠巨噬细胞样细胞系RAW 264中，液泡型（H(+)）-ATP酶（V-ATP酶）抑制剂巴弗洛霉素A(1)和 concanamycin A可增加环氧化酶（COX）-2蛋白及其mRNA的水平。c-jun N端激酶（JNK）和核因子-κB的抑制剂以及Na(+)/H(+)交换体（NHEs）的抑制剂可抑制V-ATP酶抑制剂诱导的COX-2表达。NHE抑制剂和Na(+)/Ca(2+)交换体抑制剂SN-6可抑制巴弗洛霉素A(1)诱导的JNK激活，但不抑制IkappaB-α的降解。这些结果表明，V-ATP酶抑制剂通过NHE依赖和非依赖途径诱导COX-2的表达。
