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Titolo:
Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation
Autore:
Wong, BM; Lumma, WC; Smith, AM; Sisko, JT; Wright, SD; Cai, TQ;
Indirizzi:
Merck Res Labs, Dept Lipid Biochem, Rahway, NJ 07065 USA Merck Res Labs Rahway NJ USA 07065 pt Lipid Biochem, Rahway, NJ 07065 USA Merck Res Labs, Dept Med Chem, Rahway, NJ USA Merck Res Labs Rahway NJ USA rck Res Labs, Dept Med Chem, Rahway, NJ USA
Titolo Testata:
JOURNAL OF LEUKOCYTE BIOLOGY
fascicolo: 6, volume: 69, anno: 2001,
pagine: 959 - 962
SICI:
0741-5400(200106)69:6<959:SSTCMA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
COA REDUCTASE INHIBITORS; VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE SYNTHASE; COENZYME-A REDUCTASE; ENDOTHELIAL-CELLS; RHO-GTPASES; MACROPHAGES; STABILITY; DISEASE;
Keywords:
monocytes; inhibitors; HMG-CoA reductase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
23
Recensione:
Indirizzi per estratti:
Indirizzo: Cai, TQ Merck Res Labs, Dept Lipid Biochem, RY80W-250,126 E Lincoln Ave, Rahway, NJ 07065 USA Merck Res Labs RY80W-250,126 E Lincoln Ave Rahway NJ USA 07065 USA
Citazione:
B.M. Wong et al., "Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation", J LEUK BIOL, 69(6), 2001, pp. 959-962

Abstract

Macrophages secrete matrix metalloproteinase 9 (MMP-9), an enzyme that weakens the fibrous cap of atherosclerotic plaques, predisposing them to placque rupture and subsequent ischemic events. Recent work indicates that statins strongly reduce the possibility of heart attacck. Furthermore, these compounds appear to exert beneficial effects not only by lowering plasma low-density-lipoprotein cholesterol but also by directly affecting the artery wall. To evaluate whether statins influence the proinflammatory responses of monocytic cells, we studied their effects on the chemotactic migration and MMP-9 secretion of human monocytic cell line THP-1. Simvastatin dose dependently inhibited THP-1 cell migration mediated by monocyte chemoattractant protein 1, with a 50% inhibitory concentration of about 50 nM, It also inhibited bacterial lipopolysaccharide-stimulated secretion of MMP-9, The effects of simvastatin were completely reversed by mevalonate and its derivatives, farnesylpyrophosphate and geranylgeranyl pyrophosphate, but not by ubiquinone. Additional studies revealed similar but more profound inhibitory effects with L-839,867, a specific inhibitor of geranylgeranyl transferase. However, alpha -hydroxyfarnesyl phosphonic acid, an inhibitor of farnesyl transferase, had no effect, C3 exoenzyme, a specific inhibitor of the prenylated small signaling Rho proteins, mimicked the inhibitory effects of simvastatin and L-839,867. These data supported the role of,geranylgeranylation in the migration and MMP-9 secretion of monocytes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 11:13:39