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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis.

Arachidonic acid (AA) metabolites derived from both cyclooxygenase ( COX) and lipoxygenase (LOX) pathways transduce a variety of signals related to cell growth. Here, we report that the AA LOX pathway also functions as a critical regulator of cell survival and apoptosis. Rat Walker 256 (W256) carcinosarcoma cells express 12-LOX and synthesize 12(S)- and 15(S)-hydroxyeicosatetraenoic acids as their major LOX metabolites. W256 cells transfected with 12-LOX-specific antisense oligonucleotide or antisense oligonucleotides directed to conserved regions of LOXs underwent time- and dose-dependent apoptosis. Likewise, treatment of W256 cells with various LOX but not COX inhibitors induced apoptotic cell death, which could be partially inhibited by exogenous 12(S)- or 15(S)-hydroxyeicosatetraenoic acids. The W256 cell apoptosis induced by antisense oligos and LOX inhibitors was followed by a rapid downregulation of bcl-2 protein, a dramatic decrease in the bcl-2/bax ratio, and could be suppressed by bcl-2 overexpression. In contrast, p53, which is wild type in W256 cells, did not undergo alterations during apoptosis induction. The results suggest that the LOX pathway plays an important physiological role in regulating apoptosis.[1]


  1. Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis. Tang, D.G., Chen, Y.Q., Honn, K.V. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
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