L-Xylulose reductase is involved in 9,10-phenanthrenequinone-induced apoptosis in human T lymphoma cells

Free Radical Biology & Medicine
Toshiyuki MatsunagaAkira Hara

Abstract

9,10-Phenanthrenequinone (9,10-PQ), a major component in diesel exhaust particles, is suggested to generate reactive oxygen species (ROS) through its redox cycling, leading to cell toxicity. l-Xylulose reductase (XR), a NADPH-dependent enzyme in the uronate pathway, strongly reduces alpha-dicarbonyl compounds and was thought to act as a detoxification enzyme against reactive carbonyl compounds. Here, we have investigated the role of intracellular ROS generation in apoptotic signaling in human acute T-lymphoblastic leukemia MOLT-4 cells treated with 9,10-PQ and the role of XR in the generation of ROS. Treatment with 9,10-PQ elicited not only apoptotic signaling, including mitochondrial membrane dysfunction and activation of caspases and poly(ADP-ribose) polymerase, but also intracellular ROS generation and consequent glutathione depletion. The apoptotic effects of 9,10-PQ were drastically mitigated by pretreatment with intracellular ROS scavengers, such as N-acetyl-l-cysteine, glutathione monoethyl ester, and polyethylene glycol-conjugated catalase, indicating that intracellular ROS generation is responsible for the 9,10-PQ-evoked apoptosis. Surprisingly, the ROS generation and cytotoxicity by 9,10-PQ were augmented in an XR-tra...Continue Reading

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Citations

Jan 28, 2012·Cell and Tissue Research·Toshiyuki MatsunagaAkira Hara
Dec 29, 2010·Chemico-biological Interactions·Toshiyuki MatsunagaAkira Hara
Oct 11, 2008·Chemico-biological Interactions·Satoshi EndoOssama El-Kabbani
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Nov 13, 2008·Biochemical and Biophysical Research Communications·Satoshi EndoAkira Hara
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Nov 15, 2008·Chemico-biological Interactions·Sergio PortéXavier Parés

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