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Titolo:
Angiotensin II activates the GFAT promoter in mesangial cells
Autore:
James, LR; Ingram, A; Ly, H; Thai, K; Cai, L; Scholey, JW;
Indirizzi:
Univ Toronto, Dept Med, Toronto, ON, Canada Univ Toronto Toronto ON Canada iv Toronto, Dept Med, Toronto, ON, Canada McMaster Univ, Dept Med, Hamilton, ON M5G 2C4, Canada McMaster Univ Hamilton ON Canada M5G 2C4 ed, Hamilton, ON M5G 2C4, Canada
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
fascicolo: 1, volume: 281, anno: 2001,
pagine: F151 - F162
SICI:
0363-6127(200107)281:1<F151:AIATGP>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE GFAT; ADHESION MOLECULE-1 EXPRESSION; FOSINOPRIL DECREASES LEVELS; TRANSFORMING GROWTH-FACTOR-BETA-1; TYROSINE PHOSPHORYLATION; DIABETIC NEPHROPATHY; FACTOR RECEPTOR;
Keywords:
angiotensin II; signaling; glomerulus; mesangial cells; glutamine : fructose-6-phosphate; amidotransferase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
71
Recensione:
Indirizzi per estratti:
Indirizzo: James, LR Toronto Gen Hosp, Univ Hlth Network, 13 EN-243,200 Elizabeth St,Toronto, ON M5G 2C4, Canada Toronto Gen Hosp 13 EN-243,200 Elizabeth St Toronto ON Canada M5G 2C4
Citazione:
L.R. James et al., "Angiotensin II activates the GFAT promoter in mesangial cells", AM J P-REN, 281(1), 2001, pp. F151-F162

Abstract

Expression of glutamine:fructose-6-phosphate amidotransferase (GFAT), the rate-limiting enzyme for glucose entry into the hexosamine pathway, is transcriptionally regulated. Immunohistochemical studies of human kidney biopsies demonstrate increased GFAT expression in diabetic glomeruli, but the mechanism responsible for this overexpression is unknown. Given the role of ANG II in diabetic kidney disease, we chose to study the effect of ANG II on GFAT promoter activity in mesangial cells (MC). Exposure of MC to ANG II (10(-7) M) increased GFAT promoter activity (2.5-fold), mRNA (3-fold), and protein (1.6-fold). ANG II-mediated GFAT promoter activation was inhibited bythe ANG; II type I receptor antagonist candesartan (10(-8) M) but was unaffected by the ANG II type II receptor antagonist PD-123319 (10(-8) M). The intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethaneN,N,N',N'-tetraacetic acid (10(-6) M), protein kinase C (PKC) inhibitors bisindoylmaleimide-4 (10(-6) M) and calphostin C (10(-7) M), protein tyrosine kinase (PTK) inhibitor genistein (10(-4) M), Src family kinase inhibitor PP2 (2.5 x 10(-7) M), p42/44 mitogen-activated protein kinase (MAPK) inhibitor PD-98059 (10(-5) M), and the epidermal growth factor (EGF) inhibitor AG-1478 all attenuated GFAT promoter activation by ANG II. We conclude that the GFAT promoteris activated by ANG II via the AT(1) receptor. Promoter activation is calcium dependent and PKC dependent but also involves PTK signaling pathways including Src, the EGF receptor, and p42/44 MAPK.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 01:51:51