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Titolo:
Glucocorticoid receptors are required for up-regulation of neuronal 5-lipoxygenase (5LOX) expression by dexamethasone
Autore:
Uz, T; Dwivedi, Y; Qeli, A; Peters-Golden, M; 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 Univ Michigan, Med Ctr, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 it Care Med, Ann Arbor, MI 48109 USA
Titolo Testata:
FASEB JOURNAL
fascicolo: 8, volume: 15, anno: 2001,
pagine: NIL_500 - NIL_514
SICI:
0892-6638(200106)15:8<NIL_500:GRARFU>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBELLAR GRANULE CELLS; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; GENE-EXPRESSION; PUTATIVE ROLE; ACTIVATING PROTEIN; PRIMARY CULTURES; LEUKOTRIENE C-4; BRAIN; MECHANISMS;
Keywords:
cerebellar granule neurons; leukotrienes; arachidonic acid; cerebellar granule neurons;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
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., "Glucocorticoid receptors are required for up-regulation of neuronal 5-lipoxygenase (5LOX) expression by dexamethasone", FASEB J, 15(8), 2001, pp. NIL_500-NIL_514

Abstract

5- lipoxygenase (5LOX) is the key enzyme in the synthesis of leukotrienes from arachidonic acid. Hyperglucocorticoidemia, dexamethasone, and aging up-regulate 5LOX in the brain, including the cerebellum in vivo. We studied the mechanisms of dexamethasone-triggered 5LOX upregulation in primary cultures of rat cerebellar granule neurons (CGN). We measured 5LOX mRNA and protein contents, and the formation of cysteinyl leukotrienes (LTC4, LTD4, and LTE4). The dexamethasone (0.1 muM or 1 muM)-increased 5LOX mRNA and proteincontents were already observed at 3 h of treatment, and they persisted forat least 24 h. Dexamethasone also increased the content of cysteinyl leukotrienes, assayed in the presence of 2 muM calcium ionophore A23187 and 10 muM arachidonic acid. The stimulatory effect of dexamethasone on 5LOX expression was inhibited by the glucocorticoid receptor (GR) antagonist RU486 andby reducing the CGN content of GR receptor protein with a GR-specific antisense oligonucleotide. The 5LOX mRNA half-life was longer in dexamethasone than in vehicle-treated CGNs. Our results indicate that dexamethasone increases 5LOX expression in CGNs in a GR-dependent manner and that it also increases the stability of 5LOX mRNA. Further studies are warranted to elucidate the physiologic/pathologic significance of glucocorticoid-regulated expression of 5LOX in the central nervous system.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 19:00:40