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Titolo:
Glucocorticoids stimulate inflammatory 5-lipoxygenase gene expression and protein translocation in the brain
Autore:
Uz, T; Dwivedi, Y; Savani, PD; Impagnatiello, F; Pandey, G; Manev, H;
Indirizzi:
Univ Illinois, Coll Med, Dept Psychiat, Inst Psychiat, Chicago, IL 60612 USA Univ Illinois Chicago IL USA 60612 , Inst Psychiat, Chicago, IL 60612 USA
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 2, volume: 73, anno: 1999,
pagine: 693 - 699
SICI:
0022-3042(199908)73:2<693:GSI5GE>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
MELATONIN-DEFICIENT; ACTIVATING PROTEIN; RATS; RECEPTORS; SEIZURES; CELLS;
Keywords:
5-lipoxygenase; FLAP (5-lipoxygenase-activating protein); corticosterone; dexamethasone; hippocampus; cerebellum;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Manev, H Univ Illinois, Coll Med, Dept Psychiat, Inst Psychiat, 1601 W Taylor St,MC912, Chicago, IL 60612 USA Univ Illinois 1601 W Taylor St,MC 912 Chicago IL USA 60612 12 USA
Citazione:
T. Uz et al., "Glucocorticoids stimulate inflammatory 5-lipoxygenase gene expression and protein translocation in the brain", J NEUROCHEM, 73(2), 1999, pp. 693-699

Abstract

In the brain, the expression of 5-lipoxygenase (5-LO), the enzyme responsible for the synthesis of inflammatory leukotrienes, increases during aging. Antiinflammatory drugs are currently being evaluated for the treatment of aging-associated neurodegenerative diseases such as Alzheimer's disease. Although generally considered antiinflammatory, glucocorticoids, whose production also increases during aging, are not particularly effective in this disease. In human monocytes, 5-LO mRNA content increases on exposure to the synthetic glucocorticoid dexamethasone, which prompted us to hypothesize that glucocorticoids might increase 5-LO expression in the brain as well, We treated rats for 10 days either with corticosterone (implanted subcutaneously) or with dexamethasone (injected daily); they were killed on day 10 afterpellet implantation or 24 h after the 10th dexamethasone injection. We found increased levels of 5-LO mRNA and protein in hippocampus and cerebellum of glucocorticoid-treated rats; 5-LO-activating protein (FLAP) mRNA contentwas not affected. Using western immunobloting, we also observed the concurrent translocation of 5-LO protein from cytosol to membrane, an indication of its activation. Thus, glucocorticoid-mediated up-regulation of the neuronal 5-LO pathway may contribute to rendering an aging brain vulnerable to degeneration.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 03:35:45