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Titolo:
Effects of 4,4 '-diisothyocyanatostilbene-2,2 '-disulfonic acid on Trypanosoma cruzi proliferation and Ca2+ homeostasis
Autore:
Bernardes, CF; Meyer-Fernandes, JR; Saad-Nehme, J; Vannier-Santos, MA; Peres-Sampaio, CE; Vercesi, AE;
Indirizzi:
Univ Fed Rio de Janeiro, Dept Bioquim Med, Inst Ciencias Biomed, BR-21941590 Rio De Janeiro, Brazil Univ Fed Rio de Janeiro Rio De Janeiro Brazil BR-21941590 BCeiro, Brazil Univ Estadual Campinas, Dept Patol Clin, Fac Ciencias Med, BR-13083970 Campinas, SP, Brazil Univ Estadual Campinas Campinas SP Brazil BR-13083970 BCpinas, SP, Brazil PUC Campinas, Dept Quim Bioquim, Inst Ciencias Biol & Quim, BR-13020904 Campinas, SP, Brazil PUC Campinas Campinas SP Brazil BR-13020904 BC020904 Campinas, SP, Brazil Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941590 Rio De Janeiro, Brazil Univ Fed Rio de Janeiro Rio De Janeiro Brazil BR-21941590 BCeiro, Brazil Univ Fed Rio de Janeiro, Inst Biomed, Dept Ciencias Fisiol, BR-20211040 Rio De Janeiro, Brazil Univ Fed Rio de Janeiro Rio De Janeiro Brazil BR-20211040 BCeiro, Brazil
Titolo Testata:
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
fascicolo: 5, volume: 32, anno: 2000,
pagine: 519 - 527
SICI:
1357-2725(200005)32:5<519:EO4''A>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
LEISHMANIA-MAJOR PROMASTIGOTES; PLASMA-MEMBRANE (CA2++MG2+)ATPASE; 4,4'-DIISOTHIOCYANATOSTILBENE-2,2'-DISULFONIC ACID; PHOSPHATASE-ACTIVITY; ANION TRANSPORT; MITOCHONDRIAL-MEMBRANE; CALCIUM HOMEOSTASIS; CA-2+ TRANSPORT; PH REGULATION; INHIBITION;
Keywords:
Trypanosoma cruzi epimastigote; thiol-reagent; calcium homeostasis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Meyer-Fernandes, JR Univ Fed Rio de Janeiro, Dept Bioquim Med, Inst Ciencias Biomed, CCS BlocoH Cidade Univ,Ilha Fundao, BR-21941590 Rio De Janeiro, Brazil Univ Fed Rio de Janeiro CCS Bloco H Cidade Univ,Ilha Fundao Rio De Janeiro Brazil BR-21941590 BC
Citazione:
C.F. Bernardes et al., "Effects of 4,4 '-diisothyocyanatostilbene-2,2 '-disulfonic acid on Trypanosoma cruzi proliferation and Ca2+ homeostasis", INT J BIO C, 32(5), 2000, pp. 519-527

Abstract

Cell viability requires the perfect functioning of the processes controlling ATP and Ca2+ homeostasis. It is known that cell death caused by a variety of toxins or pathological conditions is associated with a disruption of ATP and Ca2+ homeostasis. This study shows that 4,4'-diisothyocyanatostilbene-2,2 '-disulfonic acid (DIDS) inhibits Trypanosoma cruzi epimastigote cellgrowth. This thiol-reagent thiocyanate derivative was able to inhibit two ectoenzymes present in this parasite. The ecto-ATPase and ecto-phosphatase activities were inhibited in a dose-dependent manner (K-i = 47.7 and 472.5 mu M, respectively), but the 5'nucleotidase and 3'nucleotidase activities were not. DIDS uptake was approached by fluorescence microscopy. Pulse-chaseexperiments revealed the DIDS accumulation in compartments, presumably endocytic, in the posterior region of epimastigotes. In addition, we show thatthe T. cruzi mitochondria studied in permeabilized cells are able to accumulate and retain medium Ca2+ in the absence of DIDS. However, in the presence of increasing concentrations of DIDS (50-200 mu M), Ca2+ transport was inhibited in a dose-dependent manner. DIDS also caused a disruption of the mitochondrial membrane potential, in the same concentration range, thus explaining its effect on Ca2+ uptake. The presence of EGTA prevented the elimination of the mitochondrial membrane potential (Delta Psi), supporting previous data suggesting that the binding of Ca2+ to the mitochondrial membrane exposes buried thiols to react with DIDS, This thiocyanate derivative was also able to inhibit Ca2+ uptake by the endoplasmic reticulum in a dose-dependent manner. Taken together, the data presented here provide further insights into the mechanisms underlying the antiproliferative actions of DIDS inT. cruzi. (C) 2000 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 05:46:48