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Titolo:
Extracellular ATP causes apoptosis and necrosis of cultured mesangial cells via P2Z/P2X(7) receptors
Autore:
Schulze-Lohoff, E; Hugo, C; Rost, S; Arnold, S; Gruber, A; Brune, B; Sterzel, RB;
Indirizzi:
Univ Erlangen Nurnberg, Med Klin 4, Nephrol Lab, D-91054 Erlangen, GermanyUniv Erlangen Nurnberg Erlangen Germany D-91054 -91054 Erlangen, Germany
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
fascicolo: 6, volume: 44, anno: 1998,
pagine: F962 - F971
SICI:
0363-6127(199812)44:6<F962:EACAAN>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLOMERULAR CELLS; P-2Z RECEPTOR; IN-VITRO; DEATH; P53; PROLIFERATION; P2X(7); RAT; PURINOCEPTORS; FIBROBLASTS;
Keywords:
purinergic receptors; nucleotides; tumor suppressor p53;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Schulze-Lohoff, E Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Rm 4002,149 13th Harvard Univ Rm 4002,149 13th St Charlestown MA USA 02129
Citazione:
E. Schulze-Lohoff et al., "Extracellular ATP causes apoptosis and necrosis of cultured mesangial cells via P2Z/P2X(7) receptors", AM J P-REN, 44(6), 1998, pp. F962-F971

Abstract

Mesangial cells undergo cell death both by apoptosis and necrosis during glomerular disease. Since nucleotides are released from injured and destroyed cells in the glomerulus, we examined whether extracellular ATP and its receptors may regulate cell death of cultured mesangial cells. Addition of extracellular ATP (300 mu M to 5 mM) to cultured rat mesangial cells for 90 min caused a 5.8-fold increase in DNA fragmentation (terminal deoxynucleotidyl transferase assay) and a 4.2-fold increase in protein levels of the tumor suppressor p53, which is thought to regulate apoptosis. Apoptotic DNA fragmentation was confirmed by the diphenylamine assay and by staining with the DNA-specific fluorochrome Hoechst 33258. The necrotic markers, release oflactate dehydrogenase and uptake of trypan blue, were not positive before 3 h of ATP addition. The effects of ATP on DNA fragmentation and p53 expression were reproduced by the purinergic P2Z/P2X(7) receptor agonist, 3'-O-(4-benzoylbenzoyl)-ATP, and inhibited by the P2Z/P2X(7) receptor blocker, oxidized ATP. Transcripts encoding the P2Z/P2X(7) receptor were expressed by cultured mesangial cells as determined by Northern blot analysis. P2Z/P2X(7)receptor-associated pore formation in the plasma membrane was demonstratedby the Lucifer yellow assay. We conclude that activation of P2Z/P2X(7) receptors by extracellular ATP causes apoptosis and necrosis of cultured mesangial cells. Activation of purinergic P2Z/P2X(7) receptors may play a role

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Documento generato il 04/12/20 alle ore 19:46:19