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5-Lipoxygenase is required for proliferation of immature cerebellar granule neurons in vitro.

Abstract：

:Primary cultures of rat cerebellar granule neurons express 5-lipoxygenase, an enzyme from the inflammatory pathway of arachidonic acid. Outside the central nervous system (CNS) 5-lipoxygenase participates in cell proliferation. We hypothesized that 5-lipoxygenase is needed for proliferation of immature cerebellar granule neurons. Using cultures prepared from 7-day-old rat pups, we confirmed in vitro neurogenesis by immunocytolabeling with 2-bromo-5-deoxyuridine and beta-tubulin isotype III and quantified the rate of cell proliferation by assaying [3H]thymidine incorporation. We found that immature cerebellar granule neurons express large amounts of 5-lipoxygenase, and that treatment with a 5-lipoxygenase antisense, to reduce expression of this gene, decreased significantly (by 60%) the content of 5-lipoxygenase protein and effectively reduced cell proliferation. [3H]thymidine incorporation was significantly reduced by each of the three 5-lipoxygenase inhibitors we tested: AA-861 [2-(12-hydroxydodeca-5, 10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone], MK-886 (C(27)H(33)ClNO(2)S.Na), and L-655,238 [alpha-penyl-3-(2-quinolinylmethoxy)-benzenemethanol]. Their anti-proliferative effect was reversible. We propose that neuronal expression of 5-lipoxygenase is crucial for neurogenesis in vitro, and possibly also in vivo.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Uz T,Manev R,Manev H

doi

10.1016/s0014-2999(01)00924-4

keywords:

subject

Has Abstract

pub_date

2001-04-20 00:00:00

pages

15-22

issue

1-2

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(01)00924-4

journal_volume

418

pub_type

杂志文章

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