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

European Journal of Pharmacology
Tolga UzHari Manev

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 expressio...Continue Reading

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Citations

Jun 18, 2002·European Journal of Pharmacology·Hari Manev, Tolga Uz
Feb 28, 2003·Neuroscience·R HashimotoD-M Chuang
May 20, 2006·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Lei ZhangEr-Qing Wei
May 3, 2005·FEBS Letters·Manabu AriokaKatsuhiko Kitamoto
Sep 2, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·Evelin L SchaefferWagner F Gattaz
Aug 15, 2006·Neuroscience Research·Susumu KotaniTetsumori Yamashima
Sep 21, 2010·Neuroscience·H ChenH Manev
Aug 10, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·Hari ManevRadmila Manev
Jun 12, 2013·Acta Biochimica Et Biophysica Sinica·Kausik Bishayee, Anisur Rahman Khuda-Bukhsh
Sep 6, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Esther TitosJoan Rodés
Jul 2, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Baldur SveinbjörnssonPer Kogner

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