Antioxidants induce different phenotypes by a distinct modulation of signal transduction

• Published in: FEBS letters Vol. 532; no. 3; pp. 289 - 294
• Main Authors: Della Ragione, Fulvio, Cucciolla, Valeria, Criniti, Vittoria, Indaco, Stefania, Borriello, Adriana, Zappia, Vincenzo
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 18.12.2002
• Subjects: Antioxidant; Antioxidants - pharmacology; Apoptosis; DNA, Complementary - metabolism; DNA-Binding Proteins - metabolism; DPE, hydroxytyrosol; Early Growth Response Protein 1; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; HL-60 Cells; Humans; Hydroxytyrosol; Imidazoles - pharmacology; Immediate-Early Proteins; Immunohistochemistry; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Mitogen-Activated Protein Kinase Kinases - metabolism; Models, Chemical; PDTC, pyrrolidine dithiocarbamate; Phenotype; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - pharmacology; Phosphorylation; Proto-Oncogene Proteins c-jun - metabolism; Pyridines - pharmacology; Pyrrolidine dithiocarbamate; Pyrrolidines - pharmacology; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Stilbenes - pharmacology; Thiocarbamates - pharmacology; Time Factors; Transcription Factors - metabolism; Up-Regulation; Hydroxytyrosol; PDTC, pyrrolidine dithiocarbamate; Signal transduction; Resveratrol; Pyrrolidine dithiocarbamate; Antioxidant; DPE, hydroxytyrosol; Apoptosis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)03683-9

Antioxidants are known to exert a preventive activity against degenerative diseases. Here, we investigated the mechanism of action of three antioxidants: resveratrol, which causes differentiation of HL-60 cells, and hydroxytyrosol and pyrrolidine dithiocarbamate which, in the same model system, activate apoptosis. The expression profile of hydroxytyrosol-treated cells showed the up-regulation of several genes, including c-jun and egr1. Pyrrolidine dithiocarbamate activates both genes, while resveratrol increases uniquely egr1. A selective modulation of signalling pathway explained this finding. All antioxidants up-regulate Erk1/2, while only hydroxytyrosol and pyrrolidine dithiocarbamate activate c-Jun N-terminal kinase (JNK). Since JNK induces apoptosis by Bcl-2 phosphorylation, we investigated this event. Bcl-2 phosphorylation was increased by hydroxytyrosol and pyrrolidine dithiocarbamate and not by resveratrol. Our results indicate that the different phenotypical effects of antioxidants correlate with modulation of selective transduction pathways.