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Titolo:
THE ROLE OF PROTEOLYSIS IN T-CELL APOPTOSIS TRIGGERED BY CHELATION OFINTRACELLULAR ZN2+
Autore:
JIANG SN; ZHIVOTOVSKY B; BURGESS DH; GAHM A; CHOW SC; ORRENIUS S;
Indirizzi:
KAROLINSKA INST,DIV TOXICOL,INST ENVIRONM MED,BOX 210 S-17177 STOCKHOLM SWEDEN KAROLINSKA INST,DIV TOXICOL,INST ENVIRONM MED S-17177 STOCKHOLM SWEDEN
Titolo Testata:
Cell death and differentiation
fascicolo: 1, volume: 4, anno: 1997,
pagine: 39 - 50
SICI:
1350-9047(1997)4:1<39:TROPIT>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTERLEUKIN-1-BETA CONVERTING-ENZYME; DEATH GENE CED-3; ICE-LIKE PROTEASES; POLY(ADP-RIBOSE) POLYMERASE; IL-1-BETA-CONVERTING ENZYME; THYMOCYTE APOPTOSIS; MAMMALIAN HOMOLOG; NUCLEAR SCAFFOLD; IN-VITRO; CLEAVAGE;
Keywords:
THYMOCYTES; JURKAT T CELLS; TPEN; ZINC; ICE-LIKE; PROTEASES; CPP32/APOPAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
S.N. Jiang et al., "THE ROLE OF PROTEOLYSIS IN T-CELL APOPTOSIS TRIGGERED BY CHELATION OFINTRACELLULAR ZN2+", Cell death and differentiation, 4(1), 1997, pp. 39-50

Abstract

Our previous work showed that chelation of intracellular Zn2+ with N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) induces apoptosis in rat thymocytes. The molecular mechanism involved in TPEN-triggered apoptosis remains unknown, except that it is a Ca2+-independent process. In the present study, we show that TPEN is unable to induce DNA fragmentation when added to isolated thymocyte nuclei, indicating that activation of a cytoplasmic component is essential for TPEN-induced apoptosis, Since cytosolic proteases related to interleukin-1 beta-converting enzyme (ICE) are implicated as key activators of apoptos is in many different systems, we investigated the possible involvement ofsuch proteases in TPEN-induced apoptosis, We found that treatment of thymocytes with TPEN caused an early degradation of nuclear poly(ADP-ribose) polymerase (PARP) and lamin prior to DNA cleavage. This could be inhibited by Z-Val-Ala-Asp-chloromethylketone (VADcmk), an inhibitorof ICE-like proteases, but not by an inhibitor of Ca2+-regulated serine protease, Jurkat T cells also underwent extensive DNA fragmentationwhen incubated with TPEN, A cytosolic fraction, prepared from TPEN-treated Jurkat cells, produced extensive DNA fragmentation when applied to isolated thymocyte nuclei, whereas the cytoplasmic extract from untreated cells was ineffective either alone or together with TPEN, The apoptosis-inducing activity in cytosolic fraction from TPEN-treated Jurkat cells was blocked by incubating cells in the presence of VADcmk oranother inhibitor of ICE-like proteases, Ac-Asp-Glu-Val-Asp-aldehyde (DEVD-CHO), which has been found to competitively inhibit CPP32/apopain. An increase in enzyme activity that cleaves Ac-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC), a fluorogenic substrate of CPP32/apopain and Mch3 alpha, was detected in TPEN-treated thymocytes and Jurkatcells, In addition, the proteolytic cleavage of CPP32 resulting in the formation of two active fragments (p17 and p12) was observed in cytosolic extracts from TPEN-treated Jurkat cells, but not in extracts which were prepared from cells treated with TPEN in the presence of VADcmk or DEVD-CHO. Our results suggest that activation of cytosolic ICE-like proteases is an essential step in TPEN-induced apoptosis, and that CPP32/apopain is critically involved in this process.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 13:23:22