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Titolo:
CHARACTERIZATION OF AUTOCRINE INDUCIBLE PROSTAGLANDIN-H SYNTHASE-2 (PGHS-2) IN HUMAN OSTEOSARCOMA CELLS
Autore:
WONG E; DELUCA C; BOILY C; CHARLESON S; CROMLISH W; DENIS D; KARGMAN S; KENNEDY BP; OUELLET M; SKOREY K; ONEILL GP; VICKERS PJ; RIENDEAU D;
Indirizzi:
MERCK FROSST CTR THERAPEUT RES,DEPT BIOCHEM & MOL BIOL,POB 1005 POINTE CLAIRE PQ H9R 4P8 CANADA MERCK FROSST CTR THERAPEUT RES,DEPT BIOCHEM & MOL BIOL POINTE CLAIRE PQ H9R 4P8 CANADA
Titolo Testata:
Inflammation research
fascicolo: 2, volume: 46, anno: 1997,
pagine: 51 - 59
SICI:
1023-3830(1997)46:2<51:COAIPS>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYTOSOLIC PHOSPHOLIPASE A(2); SELECTIVE-INHIBITION; ENDOPEROXIDE SYNTHASE; G/H SYNTHASE-1; CYCLOOXYGENASE ISOZYMES; II PHOSPHOLIPASE-A(2); HUMAN PLATELETS; EXPRESSION; BIOSYNTHESIS;
Keywords:
PROSTAGLANDIN H SYNTHASE; CYCLOOXYGENASE; PROSTAGLANDIN; NSAIDS; INFLAMMATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
E. Wong et al., "CHARACTERIZATION OF AUTOCRINE INDUCIBLE PROSTAGLANDIN-H SYNTHASE-2 (PGHS-2) IN HUMAN OSTEOSARCOMA CELLS", Inflammation research, 46(2), 1997, pp. 51-59

Abstract

The human osteosarcoma 143.98.2 cell line was found to express high levels of prostaglandin synthase-2 (PGHS-2) without detectable levels of prostaglandin synthase-1 (PGHS-1) as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis. Maximallevels of PGHS-2 induction were attained when the cells were grown beyond confluence. The osteosarcoma cells also secrete IL-1 alpha, IL-1 beta and TNF alpha in the culture medium. PGHS-2 expression was inducible by the exogenous addition of these cytokines as well as conditioned media from auto-induced cultures and inhibitable by treatment with dexamethasone. In contrast, undifferentiated U937 cells selectively express PGHS-1 as analyzed by RT-PCR and Western blotting. The effects ofnon-steroidal anti-inflammatory drugs (NSAIDs) on the cellular PGE(2)production mediated by each isoform of human PGHS were determined using osteosarcoma and undifferentiated U937 cells. When cells were preincubated with inhibitors to allow time-dependent inhibition prior to arachidonic acid stimulation, NS-398, CGP 28238, L-745,337, SC-58125 allbehaved as potent (IC50 = 1 - 30 nM) and selective inhibitors of PGHS-2, in contrast to indomethacin, flurbiprofen or diclofenac which are potent inhibitors of both enzymes. DuP-697 and sulindac sulfide were also potent inhibitors of PGHS-2 but both compounds inhibited cellular PGHS-1 activity at higher doses (IC50 = 0.2 - 0.4 mu M). Time-dependent inhibition of PGE(2) production in osteosarcoma cells was observed for indomethacin, diclofenac and etodolac. The synthesis of PGE(2) by U937 cells was strongly dependent on exogenous arachidonic acid (100-fold stimulation) whereas confluent osteosarcoma cells also produced PGE(2) without exogenous stimulus (7-fold stimulation by arachidonic acid). Osteosarcoma cells grown beyond confluence released more PGE(2) from endogenous substrate than arachidonic acid stimulated undifferentiated U937 cells. These results indicate that osteosarcoma cells selectively express PGHS-2 with an autocrine regulation and effective utilization of endogenous arachidonic acid for PGE(2) synthesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/10/20 alle ore 20:34:49