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Titolo:
Stress-activated protein kinase/JNK activation and apoptotic induction by the macrophage P2X7 nucleotide receptor
Autore:
Humphreys, BD; Rice, J; Kertesy, SB; Dubyak, GR;
Indirizzi:
Case Western Reserve Univ, Sch Med E565, Dept Physiol & Biophys, Cleveland, OH 44106 USA Case Western Reserve Univ Cleveland OH USA 44106 Cleveland, OH 44106 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 35, volume: 275, anno: 2000,
pagine: 26792 - 26798
SICI:
0021-9258(20000901)275:35<26792:SPKAAA>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
N-TERMINAL KINASE; JUN NH2-TERMINAL KINASE; EXTRACELLULAR ATP; MEDIATED ACTIVATION; P2X(7) RECEPTOR; CELL-DEATH; KAPPA-B; SIGNAL-TRANSDUCTION; POTASSIUM-DEPLETION; P2Z PURINORECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Dubyak, GR Case Western Reserve Univ, Sch Med E565, Dept Physiol & Biophys, 10900 Euclid Ave, Cleveland, OH 44106 USA Case Western Reserve Univ 10900Euclid Ave Cleveland OH USA 44106
Citazione:
B.D. Humphreys et al., "Stress-activated protein kinase/JNK activation and apoptotic induction by the macrophage P2X7 nucleotide receptor", J BIOL CHEM, 275(35), 2000, pp. 26792-26798

Abstract

In human and rodent macrophages, activation of the P2X7 nucleotide receptor stimulates interleukin-1 beta processing and release, apoptosis, and killing of intracellular Mycobacterium tuberculosis. Signaling pathways downstream of this ionotropic ATP receptor are poorly understood Here we describe the rapid activation of the stress-activated protein kinase (SAPK)/JNK pathway in BAC1 murine macrophages stimulated by extracellular ATP, Brief exposure of the cells to ATP (10-30 min) was sufficient to trigger a rapid accumulation of activated SAPK that was then sustained for >120 min. Several observations indicated that the P2X7 receptor mediated this effect. 1) ATP and3'-O-(4-benzoyl)benzoyl-ATP were the only agonistic nucleotides, 2) The effect was inhibited by oxidized ATP and the isoquinoline KN-62, two known P2X7 receptor antagonists. 3) ATP-induced SAPK activation could be recapitulated in P2X7 receptor-transfected HEK293 cells, but not in wild-type HEK293 cells. Because P2X7 receptor stimulation can rapidly activate caspase family proteases that have been implicated in the induction of the SAPK pathway,we investigated whether ATP-dependent SAPK activation involved such proteases, Brief exposure of BAC1 macrophages to extracellular ATP induced DNA fragmentation, alpha-fodrin breakdown, and elevated levels of caspase-3-type activity. Asp-Glu-Val-Asp-cho a caspase-3 inhibitor, inhibited ATP-induced DNA fragmentation and alpha-fodrin proteolysis, but had no effect on ATP-induced SAPK activation. Tyr-Val-Ala-Asp-chloromethyl ketone, a caspase-1 inhibitor, prevented ATP-induced release of processed interleukin-1 beta, but not ATP-dependent SAPK activity. We conclude that activation of ionotropic P2X7 nucleotide receptors triggers a strong activation of SAPK via a pathway independent of caspase-1- or caspase-3-like proteases.

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Documento generato il 02/12/20 alle ore 04:53:23