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Titolo:
3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) induces caspase-dependent apoptosis in mononuclear cells
Autore:
Hashimoto, T; Ashida, H; Sano, T; Furuyashiki, T; Hatanaka, Y; Minato, K; Mizuno, M; Nomura, K; Kumatori, A; Kanazawa, K; Danno, G;
Indirizzi:
Kobe Univ, Grad Sch Sci & Technol, Div Life Sci, Kobe, Hyogo 6578501, Japan Kobe Univ Kobe Hyogo Japan 6578501 v Life Sci, Kobe, Hyogo 6578501, Japan Kobe Univ, Fac Agr, Dept Biofunct Chem, Nada Ku, Kobe, Hyogo 6578501, Japan Kobe Univ Kobe Hyogo Japan 6578501 m, Nada Ku, Kobe, Hyogo 6578501, Japan Kobe Univ, Ctr Cooperat Res & Dev, Kobe, Hyogo 6578501, Japan Kobe Univ Kobe Hyogo Japan 6578501 Res & Dev, Kobe, Hyogo 6578501, Japan Nagasaki Univ, Inst Trop Med, Dept Biochem, Nagasaki 8528523, Japan Nagasaki Univ Nagasaki Japan 8528523 pt Biochem, Nagasaki 8528523, Japan
Titolo Testata:
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
fascicolo: 1-2, volume: 1539, anno: 2001,
pagine: 44 - 57
SICI:
0167-4889(20010528)1539:1-2<44:3(IC>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRYPTOPHAN PYROLYSIS PRODUCTS; DRUG-INDUCED APOPTOSIS; CYTOCHROME-C RELEASE; BCL-X-L; HETEROCYCLIC AMINES; METABOLIC-ACTIVATION; HUMAN-LYMPHOCYTES; SEQUENTIAL ACTIVATION; SEROTONIN TRANSPORTER; PROTEASE CASCADE;
Keywords:
heterocyclic amine; 3-amino-1,4-dimethyl-5H-pyrido[4.3-b]indole apoptosis; caspase; mononuclear cell; rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Ashida, H Kobe Univ, Grad Sch Sci & Technol, Div Life Sci, Kobe, Hyogo 6578501, Japan Kobe Univ Kobe Hyogo Japan 6578501 , Kobe, Hyogo 6578501, Japan
Citazione:
T. Hashimoto et al., "3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) induces caspase-dependent apoptosis in mononuclear cells", BBA-MOL CEL, 1539(1-2), 2001, pp. 44-57

Abstract

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), one of the tryptophan pyrolysates, is a dietary carcinogen and is formed in cooked meat and fish in our daily diet. Trp-P-1 will affect the cells in the blood circulation system before it causes carcinogenicity in target organs such as the liver. In this study, the cytotoxicity of Trp-P-1 was investigated in mononuclear cells (MNCs) from blood. Trp-P-1 (10-15 CIM) decreased cell viability and induced apoptosis characterized both by morphological changes and by DNA fragmentation 4 h after treatment. DNA fragmentation was also observed following treatment at 1 nM after 24 h in culture. This result suggested that apoptosis would occur in the body following unexpected intake of foods containing Trp-P-1. To determine the mechanism of apoptosis, we investigated theactivation of the caspase cascade in MNCs. Trp-P-1 (10-15 muM) activated the caspase cascade, i.e. the activity of caspase-3,-6,-7,-8 and -9 increased dose-dependently using peptide substrates, the active forms of caspase-3,-8 and -9 were detected by immunoblotting, and cleavage of poly(ADP-ribose) polymerase and protein kinase C-delta as the intracellular substrates forcaspases was observed. A peptide inhibitor of caspase-8 completely suppressed activation of all other caspases, while an inhibitor of caspase-9 did not. These results indicated that caspase-8 may act as an apical caspase in the Trp-P-1-activated cascade. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 04:22:18