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Titolo:
ADENOSINE STIMULATES DNA FRAGMENTATION IN HUMAN THYMOCYTES BY CA2-MEDIATED MECHANISMS()
Autore:
SZONDY Z;
Indirizzi:
DEBRECEN UNIV MED,DEPT BIOCHEM H-4012 DEBRECEN HUNGARY
Titolo Testata:
Biochemical journal
, volume: 304, anno: 1994,
parte:, 3
pagine: 877 - 885
SICI:
0264-6021(1994)304:<877:ASDFIH>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROGRAMMED CELL-DEATH; ENDOGENOUS ENDONUCLEASE ACTIVATION; ADENYLATE-CYCLASE ACTIVATION; GUINEA-PIG ATRIAL; CYCLIC-AMP; IMMATURE THYMOCYTES; RECEPTOR COMPLEX; CONCANAVALIN-A; LYMPHOCYTES-T; CALCIUM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
56
Recensione:
Indirizzi per estratti:
Citazione:
Z. Szondy, "ADENOSINE STIMULATES DNA FRAGMENTATION IN HUMAN THYMOCYTES BY CA2-MEDIATED MECHANISMS()", Biochemical journal, 304, 1994, pp. 877-885

Abstract

Incubation of human thymocytes with an optimum concentration of adenosine and its receptor site agonist, 2-chloroadenosine, induced increases in intracellular cyclic AMP (cAMP) (from a resting 0.6 +/- 0.1 to 4.1 +/- 0.2 pmol/10(7) cells within 5 min) and Ca2+ (from the resting 85 +/- 7 nM to a peak of 210 +/- 25 nM) levels and resulted in internucleosomal DNA fragmentation and cell death (apoptosis). Other adenosineanalogues were also effective at inducing DNA fragmentation, the order of potency being oxyethylphenylethylamino)-5'-carboxyamidoadenosine < 5'-(N-ethylcarboxamide)adeno sine less than or equal to cyclopentyladenosine < 2-chloroadenosine (2-CA). 2-CA treatment (with an optimum concentration of 40 mu M) selectively depleted a thymocyte subpopulation (15-20 % of the total cells) which expressed higher levels of the CD3 molecule and which was found mainly in the CD4(+)CD8(+) double positive immature thymocyte population. DNA fragmentation was prevented by the addition of actinomycin D or cycloheximide to the thymocyte suspension, indicating that this process required both mRNA and protein synthesis. Endonuclease activation and cell killing were dependent on an early, sustained increase in cytosolic Ca2+ concentration, most of which was of extracellular origin and was a result of an adenosine-inducedinositol trisphosphate release. Other agents known to elevate intracellular cAMP levels by different mechanisms failed to induce similar DNA fragmentation, but enhanced the effect of adenosine. This suggested a supporting role for cAMP in adenosine-induced DNA fragmentation. Phorbol dibutyrate, a protein kinase C activator, previously shown to inhibit Ca2+-dependent DNA fragmentation and cell killing in human thymocytes [McConkey, Hartzell, Jondal and Orrenius (1989) J. Biol. Chem. 264, 13399-13402], at 60 ng/ml concentration also prevented adenosine-induced DNA fragmentation when added prior to adenosine. This suggested a complex cross-talk between the adenosine-triggered signal transduction cascade and the activation state of protein kinase C in regulating apoptosis of human thymocytes.

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Documento generato il 29/09/20 alle ore 20:17:10