Involvement of intracellular oxidative stress-sensitive pathway in phloxine B-induced photocytotoxicity in human T lymphocytic leukemia cells.

Abstract

We investigated the molecular mechanisms underlying phloxine B (PhB)-induced photocytotoxicity in human T lymphocytic leukemia Jurkat cells. In addition to apoptosis-related biochemical events, photo-irradiated PhB generated intracellular reactive oxygen species (ROS), induced phosphorylation of c-Jun-N-terminal kinase (JNK) in an oxidative stress-dependent manner and up-regulated the gene expression of interferon (IFN)-γ, an inducer of diverse apoptosis-related molecules in activated T cells. PhB-induced apoptosis was significantly inhibited by N-acetyl-l-cysteine, but not by catalase, indicating that ROS generation occurred intracellularly, and by SP600125 and AG490, specific inhibitors of JNK and IFN-γ signaling, respectively, confirming their roles in the apoptotic pathway. IFN-γ up-regulation was also inhibited by SP600125, indicating that it was downstream of JNK activation. These results suggest that PhB-induced apoptosis in Jurkat cells partially involves the intracellular oxidative stress-sensitive and T cell-specific IFN-γ pathway. These data present a novel insight into the mechanisms of photocytotoxicity induced by artificial food colorants in human T lymphocytic leukemia cells.

• Authors: Hang Qi, Beiwei Zhu, Naomi Abe, Yuko Shin, Yoshiyuki Murata, Yoshimasa Nakamura
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 50 Issue 6 Pg. 1841-7 (Jun 2012) ISSN: 1873-6351 [Electronic] England
• PMID: 22440610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• 2',7'-dichlorodihydrofluorescein diacetate
• Fluoresceins
• Fluorescent Dyes
• Indicators and Reagents
• PHB protein, human
• Prohibitins
• Interferon-gamma
• Catalase
• JNK Mitogen-Activated Protein Kinases
• Caspase 3
• Eosine I Bluish

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Caspase 3 (metabolism)
• Catalase (metabolism)
• DNA Fragmentation
• Dermatitis, Phototoxic (pathology)
• Eosine I Bluish (toxicity)
• Fluoresceins
• Fluorescent Dyes (toxicity)
• Humans
• Indicators and Reagents
• Interferon-gamma (metabolism)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Jurkat Cells
• Leukemia, T-Cell (pathology)
• Light
• Oxidative Stress (drug effects)
• Phosphorylation
• Prohibitins
• Real-Time Polymerase Chain Reaction
• Signal Transduction (drug effects)