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Titolo:
Molecular basis for a link between complement and the vascular complications of diabetes
Autore:
Acosta, J; Hettinga, J; Fluckiger, R; Krumrei, N; Goldfine, A; Angarita, L; Halperin, J;
Indirizzi:
Harvard Univ, Sch Med, Lab Membrane Transport, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Membrane Transport, Boston, MA 02115 USA Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 Dept Med, Boston, MA 02115 USA Joslin Diabet Ctr, Boston, MA 02115 USA Joslin Diabet Ctr Boston MA USA 02115 in Diabet Ctr, Boston, MA 02115 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 10, volume: 97, anno: 2000,
pagine: 5450 - 5455
SICI:
0027-8424(20000509)97:10<5450:MBFALB>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEMBRANE-ATTACK-COMPLEX; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; REGULATORY PROTEIN CD59; FUNCTIONAL-CHARACTERIZATION; NONENZYMATIC GLYCOSYLATION; BIOLOGIC ACTIVITY; HUMAN-URINE; CELLS; MELLITUS; SITES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Halperin, J Harvard Univ, Sch Med, Lab Membrane Transport, 240 Longwood Ave,C1-607, Boston, MA 02115 USA Harvard Univ 240 Longwood Ave,C1-607 Boston MA USA 02115 5 USA
Citazione:
J. Acosta et al., "Molecular basis for a link between complement and the vascular complications of diabetes", P NAS US, 97(10), 2000, pp. 5450-5455

Abstract

Activated terminal complement proteins C5b to C9 form the membrane attack complex (MAC) pore. Insertion of the MAC into endothelial cell membranes causes the release of growth factors that stimulate tissue growth and proliferation. The complement regulatory membrane protein CD59 restricts MAC formation. Because increased cell proliferation characterizes the major chronic vascular complications of human diabetes and because increased glucose levels in diabetes cause protein glycation and impairment of protein function, we investigated whether glycation could inhibit CD59. Glycation-inactivation of CD59 would cause increased MAC deposition and MAC-stimulated cell proliferation. Here, we report that (i) human CD59 is glycated in vivo, (ii) glycated human CD59 loses its MAC-inhibitory function, and (iii) inactivationof CD59 increases MAC-induced growth factor release from endothelial cells. We demonstrate by site-directed mutagenesis that residues K41 and H44 form a preferential glycation motif in human CD59. The presence of this glycation motif in human CD59, but not in CD59 of other species, may help explainthe distinct propensity of humans to develop vascular proliferative complications of diabetes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 05:00:09