Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells.
alpha-Lipoic acid (LA) is a naturally-occurring micronutrient that has been actively investigated for the treatment and management of various chronic medical conditions including neurodegenerative diseases, diabetes and hepatic disorders. However, relatively few studies have examined the effects of LA as a chemopreventive agent, particularly in regard to its ability to modulate homeostasis of oxidoreductive state and to regulate detoxification enzymes such as quinone reductase NQO1 in LA-responsive cells. We tested the hypothesis that LA affects the intracellular redox status and induces NQO1 expression using the human promyelocytic HL-60 leukemia cells. We showed that treatment by LA maintains HL-60 cells in a relatively reduced state, supported by the dose/time-dependent increase in the activities of glutathione peroxidase and glutathione reductase and decrease in the activity of catalase. Moreover, LA significantly increased the activity and protein expression of NQO1. The induction of NQO1 was accompanied by the nuclear accumulation of transcription factor Nrf2, which was correlated with a decreased level of Nrf2 in the cytosol as well as the concomitant reduction in the expression of cytoplasmic repressor of Nrf2, Keap1.
Elangovan
Selvakumar
S
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Hsieh
Tze-Chen
TC
D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D021381:Protein Transport; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D008063:Thioctic Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005980:Glutathione Reductase