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Titolo:
CYTOPROTECTIVE EFFECTS OF ADRENOMEDULLIN IN GLOMERULAR CELL INJURY - CENTRAL ROLE OF CAMP SIGNALING PATHWAY
Autore:
CHINI EN; CHINI CCS; BOLLIGER C; JOUGASAKI M; GRANDE JP; BURNETT JC; DOUSA TP;
Indirizzi:
MAYO CLIN & MAYO FDN,MAYO MED SCH,DEPT PHYSIOL BIOPHYS & MED & LAB MED ROCHESTER MN 55905 MAYO CLIN & MAYO FDN,MAYO MED SCH,DEPT PHYSIOL BIOPHYS & MED & LAB MED ROCHESTER MN 55905
Titolo Testata:
Kidney international
fascicolo: 4, volume: 52, anno: 1997,
pagine: 917 - 925
SICI:
0085-2538(1997)52:4<917:CEOAIG>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; ACTIVATED PROTEIN-KINASE; TUMOR-NECROSIS-FACTOR; RAT MESANGIAL CELLS; GROWTH-FACTOR; CYCLIC-AMP; ALPHA PRODUCTION; NADPH OXIDASE; PHOSPHODIESTERASE; INHIBITION;
Keywords:
ADRENOMEDULLIN; REACTIVE OXYGEN METABOLITES; MESANGIAL CELLS; CAMP-PKA SIGNALING PATHWAY; INJURY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
E.N. Chini et al., "CYTOPROTECTIVE EFFECTS OF ADRENOMEDULLIN IN GLOMERULAR CELL INJURY - CENTRAL ROLE OF CAMP SIGNALING PATHWAY", Kidney international, 52(4), 1997, pp. 917-925

Abstract

Activation of cAMP signaling pathway was shown to inhibit some pathobiologic processes in mesangial cells (MC). We investigated whether adrenomedullin (ADM), a potent agonist of adenylate cyclase, is synthesized in MC and whether it can, via cAMP, suppress the generation of reactive oxygen metabolites (ROM) and proliferation of cells in glomeruli. With the use of an immunohistologic technique ADM was detected in mesangial and microvascular areas of rat glomeruli. MC grown in primary culture synthesized ADM, and the synthesis was stimulated by TNF alpha and IL-1 beta but not by PDGF and EGF. ADM inhibited ROM generation inMC dose-dependently and caused in situ activation of protein kinase A(PKA). In macrophages (cell line J774) ROM generation was about four times higher than in MC and was inhibited by ADM in a similar way as in MC. The rate of MC proliferation, measured by [H-3]-incorporation, and the activity of mitogen-activated protein kinase (MAPK) stimulated by PDGF and EGF were dose-dependently inhibited by ADM; the maximum inhibition (at 10 nM ADM) was about -80%. Mitogenesis of MC and MAPK activity when stimulated to a similar extent by endothelin (ET-1) was inhibited by ADM to a significantly (P < 0.01) lesser degree (-30%). Further, ADM inhibited PDGF-stimulated mitogenesis and activation of MAPK in cultured vascular smooth muscle cells (VSMC). The inhibition of PDGF-activated MAPK by ADM in VSMC was reversed by the protein kinase A (PKA) inhibitor, H89. Taken together, results indicate that adrenomedullin (ADM) generated in mesangial cells (MC) can suppress, via activation of the cAMP-protein kinase A (PKA) signaling pathway, reactive oxygen metabolites (ROM) generation in MC and infiltrating macrophages as well as mitogen-activated protein kinase (MAPK)-mediated mitogenesis in MC and vascular smooth muscle cells (VSMC). We suggest that intraglomerular ADM may serve as a cytoprotective autacoid that suppresses pathobiologic processes evoked by immune-inflammatory injury of glomeruli.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 06:29:38