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Titolo:
SPECIFIC-INHIBITION OF EIF-5A AND COLLAGEN HYDROXYLATION BY A SINGLE-AGENT - ANTIPROLIFERATIVE AND FIBROSUPPRESSIVE EFFECTS ON SMOOTH-MUSCLE CELLS FROM HUMAN CORONARY-ARTERIES
Autore:
MCCAFFREY TA; POMERANTZ KB; SANBORN TA; SPOKOJNY AM; DU BH; PARK MH; FOLK JE; LAMBERG A; KIVIRIKKO KI; FALCONE DJ; MEHTA SB; HANAUSKEABEL HM;
Indirizzi:
CORNELL UNIV,COLL MED,DEPT MED,DIV HEMATOL ONCOL,RM C-608,1300 YORK AVE NEW YORK NY 10021 CORNELL UNIV,NEW YORK HOSP,COLL MED,DEPT MED,DIV HEMATOL ONCOL NEW YORK NY 10021 CORNELL UNIV,NEW YORK HOSP,COLL MED,DEPT PATHOL CELL BIOL & ANAT NEW YORK NY 10021 CORNELL UNIV,NEW YORK HOSP,COLL MED,CARDIAC CATHETERIZAT LAB NEW YORKNY 10021 CORNELL UNIV,NEW YORK HOSP,COLL MED,DEPT PEDIAT NEW YORK NY 10021 NIDR,CELLULAR DEV & ONCOL LAB BETHESDA MD 20892 UNIV OULU,DEPT MED BIOCHEM OULU FINLAND
Titolo Testata:
The Journal of clinical investigation
fascicolo: 2, volume: 95, anno: 1995,
pagine: 446 - 455
SICI:
0021-9738(1995)95:2<446:SOEACH>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSFORMING GROWTH FACTOR-BETA-1; PROLYL 4-HYDROXYLASE; EXTRACELLULAR-MATRIX; I PROCOLLAGEN; BINDING; PROTEIN; 2-OXOGLUTARATE; INJURY; SITE; GROWTH-FACTOR-BETA-1;
Keywords:
VASCULAR SMOOTH MUSCLE; CELL DIVISION; COLLAGEN; HYDROXYLASES; MIMOSINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
55
Recensione:
Indirizzi per estratti:
Citazione:
T.A. Mccaffrey et al., "SPECIFIC-INHIBITION OF EIF-5A AND COLLAGEN HYDROXYLATION BY A SINGLE-AGENT - ANTIPROLIFERATIVE AND FIBROSUPPRESSIVE EFFECTS ON SMOOTH-MUSCLE CELLS FROM HUMAN CORONARY-ARTERIES", The Journal of clinical investigation, 95(2), 1995, pp. 446-455

Abstract

Restenosis occurs in 35% of patients within months after balloon angioplasty, due to a fibroproliferative response to vascular injury. These studies describe a combined fibrosuppressive/antiproliferative strategy on smooth muscle cells cultured from human primary atheroscleroticand restenotic coronary arteries and from normal rat aortas. L-Mimosine suppressed the posttranslational hydroxylation of the precursors for collagen and for eukaryotic initiation factor-5A (eIF-5A) by directly inhibiting the specific protein hydroxylases involved,prolyl 4-hydroxylase (E.C. 1.14.11.2) and deoxyhypusyl hydroxylase (E.C. 1.14.99.29), respectively. Inhibition of deoxyhypusyl hydroxylation correlated with a dose-dependent inhibition of DNA synthesis. Inhibition of prolyl hydroxylation caused a dose-dependent reduction in the secretion of hydroxyproline-containing protein and decreased the formation of procollagen types I and III. The antifibroproliferative action could not be attributed to nonspecific or toxic effects of mimosine, appeared to be selective for the hydroxylation step in the biosynthesis of the procollagens and of eIF-5A, and was reversible upon removal of the compound. The strategy of targeting these two protein hydroxylases has important implications for the pathophysiology of restenosis and for the development of agents to control fibroproliferative diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 07:49:08