Li Y, Maher P, Schubert D
Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Neuron. 1997 Aug;19(2):453-63. doi: 10.1016/s0896-6273(00)80953-8.
An early and highly specific decrease in glutathione (GSH) in the substantia nigra is associated with Parkinson's disease, and low levels of GSH lead to the degeneration of cultured dopaminergic neurons. Using immature cortical neurons and a clonal nerve cell line, it is shown that a decrease in GSH triggers the activation of neuronal 12-lipoxygenase (12-LOX), which leads to the production of peroxides, the influx of Ca2+, and ultimately to cell death. The supporting evidence includes: 1) inhibitors of arachidonate metabolism and 12-LOX block cell death induced by GSH depletion; 2) there is an increase in 12-LOX activity and a membrane translocation in HT22 cells, and an induction of the enzyme in primary cortical neurons following the reduction of GSH; 3) 12-LOX is directly inhibited by GSH; and 4) exogenous arachidonic acid potentiates cell death. These data show that the LOX pathway is a critical intermediate in at least some forms of neuronal degeneration.
黑质中谷胱甘肽（GSH）早期且高度特异性的减少与帕金森病相关，而低水平的GSH会导致培养的多巴胺能神经元退化。利用未成熟的皮质神经元和克隆神经细胞系，研究表明GSH的减少会触发神经元12 - 脂氧合酶（12 - LOX）的激活，这会导致过氧化物的产生、Ca2 + 的内流，并最终导致细胞死亡。支持证据包括：1）花生四烯酸代谢抑制剂和12 - LOX可阻断GSH耗竭诱导的细胞死亡；2）HT22细胞中12 - LOX活性增加且发生膜转位，在原代皮质神经元中GSH减少后该酶被诱导；3）GSH可直接抑制12 - LOX；4）外源性花生四烯酸会增强细胞死亡。这些数据表明，脂氧合酶途径至少在某些形式的神经元退化中是关键的中间环节。
