期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 587, 期 1-3, 页码 187-195出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.02.031
关键词
Kv3.4; 15-lipoxygenase; 15-hydroxyeicosatetraenoic acid; subacute hypoxia; pulmonary arterial smooth muscle cells
We have previously reported that subacute hypoxia activates lung 15-lipoxygenase (15-LOX), which catalyzes arachidonic acid to produce 15-HETE, leading to constriction of neonatal rabbit pulmonary arteries. Subacute hypoxia suppresses Kv3.4 channel expression and results in an inhibition of whole-cell K+ currents (I-K). Although the Kv channel inhibition is likely to be mediated through 15-HETE, direct evidence is still lacking. To reveal the role of the 15-LOX/15-HETE pathway in the hypoxia-induced down-regulation of Kv3.4 channel expression and inhibition of I-K, we performed studies using 15-LOX blockers, whole-cell patch-clamp, semi-quantitative PCR, ELISA and Western blot analysis. We found that Kv3.4 channel expression at the mRNA and protein levels was greatly up-regulated in pulmonary arterial smooth muscle cells after blockade of 15-LOX by CDC or NDGA. The 15-LOX blockade also partially restored I-K. In comparison, 15-HETE had a stronger effect than 12-HETE on the expression of Kv3.4 channels. 5-HETE had no noticeable effect on Kv3.4 channel expression. These data indicate that the 15-LOX pathway via its metabolite, 15-HETE, seems to play a role in the down-regulation of Kv3.4 expression and I-K inhibition after subacute hypoxia. (C) 2008 Elsevier B.V. All rights reserved.
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