Inflammatory 5-LOX mRNA and protein are increased in brain of aging rats

5-Lipoxygenase (5-LOX) is the key enzyme in the synthesis of leukotrienes, inflammatory mediators of arachidonic acid. 5-LOX is also expressed in neur ons (in particular in the hippocampus and the cerebellum), and it seems to be capable of promoting neurodegeneration. Recently, we observed greater 5- LOX mRNA content in the hippocampus of older (24 months) than younger (2 mo nths) rats. In this study, we measured in the hippocampus and the cerebellu m of younger and older male F344 rats the contents of: 5-LOX mRNA, FLAP (5- LOX activating protein) mRNA, and 5-LOX protein. By using a quantitative re verse transcription/polymerase chain reaction (PCR) (RT-PCR) with internal standards we found that 5-LOX but not FLAP mRNA content is greater (both in hippocampus and cerebellum) of older than younger rats. By using quantitat ive Western immunoblotting, we found a greater content of 5-LOX protein in the hippocampus and the cerebellum of older rats; we also established that the membrane/cytosol 5-LOX content ratio is larger in the brains of older t han younger rats (statistically significant in the cerebellum). The latter can be considered an indication of 5-LOX translocation/activation during ag ing. Together these results suggest that aging increases both neuronal 5-LO X expression and protein translocation, and indicate that the 5-LOX system might play a significant role in the pathobiology of aging-associated neuro degenerative diseases. (C) 2000 Elsevier Science Inc. All rights reserved.