Neurogenesis and neuroprotection in the adult brain. A putative role for 5-lipoxygenase?
5-Lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) are two enzymes that are critical for the synthesis of eicosanoids, the inflammatory metabolites of arachidonic acid. Both 5-LOX and COX-2 are expressed in the brain, including in CNS neurons. The physiologic role of these proteins in neuronal functioning is not clear. In non-neuronal tissues these two enzymes often assume similar roles: in addition to their function in inflammation, 5-LOX and COX-2 appear to be associated with cell proliferation, that is, with tumor growth. High 5-LOX expression has been noticed in the proliferating brain or pancreatic tumor cells; reduction in tumor cell proliferation and/or destruction of tumor cells was achieved with 5-LOX inhibitors. Proliferation of immature neurons/neuroblasts is an important component of mitotic neurogenesis. We investigated the role of 5-LOX in proliferation using cultures of human neuronal precursor cells, NT2. We found that these cells express 5-LOX mRNA and we used 3H-thymidine incorporation as a measure of cell proliferation; this was reduced by treating the cultures with 5-LOX inhibitor AA-861. We propose that the 5-LOX pathway plays a crucial role in mitotic neurogenesis. Additional studies should explore whether 5-LOX may participate in neurogenesis related pathologies and whether it should be considered a target for procedures aimed at altering neurogenesis for therapeutic purposes.
Manev
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H
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, IL 60612, USA. HManev@psych.uic.edu
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Manev
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Zhang
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D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects* / Q000378:metabolism; D016227:Benzoquinones / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism
D016227:Benzoquinones; D016859:Lipoxygenase Inhibitors; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D001094:Arachidonate 5-Lipoxygenase