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Titolo:
ROLE OF PROTEIN-KINASE-C AND CYCLIC-AMP PROTEIN-KINASE-A IN HIGH GLUCOSE-STIMULATED TRANSCRIPTIONAL ACTIVATION OF COLLAGEN ALPHA-1(IV) IN GLOMERULAR MESANGIAL CELLS
Autore:
ZIYADEH FN; FUMO P; RODENBERGER CH; KUNCIO GS; NEILSON EG;
Indirizzi:
UNIV PENN,SCH MED,RENAL ELECTROLYTE & HYPERTENS DIV,DEPT MED,PENN CTRMOL STUDIES KIDNEY DIS PHILADELPHIA PA 19104
Titolo Testata:
Journal of diabetes and its complications
fascicolo: 4, volume: 9, anno: 1995,
pagine: 255 - 261
SICI:
1056-8727(1995)9:4<255:ROPACP>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROXIMAL TUBULE CELLS; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; BIDIRECTIONAL PROMOTER; DIABETIC NEPHROPATHY; MESSENGER-RNA; PROLIFERATION; GENE; MYOINOSITOL; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
F.N. Ziyadeh et al., "ROLE OF PROTEIN-KINASE-C AND CYCLIC-AMP PROTEIN-KINASE-A IN HIGH GLUCOSE-STIMULATED TRANSCRIPTIONAL ACTIVATION OF COLLAGEN ALPHA-1(IV) IN GLOMERULAR MESANGIAL CELLS", Journal of diabetes and its complications, 9(4), 1995, pp. 255-261

Abstract

The elevated mRNA levels encoding matrix components in glomeruli isolated from streptozotocin-induced diabetic rats provide evidence that stimulation of matrix synthesis is important in early phases of diabetic glomerulopathy. We and others have demonstrated that high glucose stimulates collagen mRNA levels in short-term mesangial cell culture, Totest whether transcriptional activation is operative and to gain insights into the underlying mechanisms, we studied a murine mesangial cell line stably transfected with a minigene expressing luciferase drivenby 5'-flanking and first-intron regions of the (alpha 1(IV) gene. High glucose stimulated luciferase activity dose and time dependently, with optimal stimulation (two-fold) achieved after 48 h in 450 mg/dL glucose (G450) versus 100 mg/dL (G100). We next tested the involvement ofprotein kinase C (PKC) because high glucose has been shown to stimulate de novo synthesis of diacylglycerol (DAG), Increasing PKC activity by treatment with a DAG analogue or active phorbol ester stimulated luciferase activity preferentially in G100; addition of the PKC inhibitors staurosporine or calphostin C markedly inhibited luciferase activity preferentially in G450. Thus high glucose promotes transcriptional activity of alpha 1(IV) gene through PKC activation, We also tested theinvolvement of protein kinase A (PKA), Intracellular cyclic AMP levels were increased two fold after 48 h in G450 versus G100, and additionof 8-Br-cAMP (0.1 mM) preferentially stimulated luciferase activity by almost three fold in G100 versus only 1.2-fold in G450, Hence, the signal-transduction mechanisms underlying the transcriptional activation of alpha 1(IV) gene in mesangial cells by high glucose are mediated by pathways involving the PKC system and possibly the cAMP/PKA system

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 19:52:33