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 neurons (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 months) rats. In this study, we measured in the hippocampus and the cerebellum 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 reverse 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 quantitative 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 than younger rats (statistically significant in the cerebellum). The latter can be considered an indication of 5-LOX translocation/activation during aging. Together these results suggest that aging increases both neuronal 5-LOX expression and protein translocation, and indicate that the 5-LOX system might play a significant role in the pathobiology of aging-associated neurodegenerative diseases.
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The Psvchiatric Institute, University of Illinois at Chicago, IL 60612, USA.
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Manev
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D058927:5-Lipoxygenase-Activating Proteins; D000375:Aging / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology* / Q000276:immunology; D017931:DNA Primers; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006624:Hippocampus / Q000201:enzymology* / Q000276:immunology; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D058927:5-Lipoxygenase-Activating Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D015289:Leukotrienes; D008565:Membrane Proteins; D012333:RNA, Messenger; D001094:Arachidonate 5-Lipoxygenase