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Increased Glutathione Synthesis Following Nrf2 Activation by Vanadyl Sulfate in Human Chang Liver Cells
School of Medicine, Jeju National University, Jeju 690-756, Korea
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea
Department of Biomaterials, DNA Repair Center, Chosun University, Gwangju 501-759, Korea
* Author to whom correspondence should be addressed.
Received: 1 September 2011; in revised form: 3 November 2011 / Accepted: 21 November 2011 / Published: 5 December 2011
Abstract: Jeju ground water, containing vanadium compounds, was shown to increase glutathione (GSH) levels as determined by a colorimetric assay and confocal microscopy. To investigate whether the effects of Jeju ground water on GSH were specifically mediated by vanadium compounds, human Chang liver cells were incubated for 10 passages in media containing deionized distilled water (DDW), Jeju ground water (S1 and S3), and vanadyl sulfate (VOSO4). Vanadyl sulfate scavenged superoxide anion, hydroxyl radical and intracellular reactive oxygen species. Vanadyl sulfate effectively increased cellular GSH level and up-regulated mRNA and protein expression of a catalytic subunit of glutamate cysteine ligase (GCLC), which is involved in GSH synthesis. The induction of GCLC expression by vanadyl sulfate was found to be mediated by transcription factor erythroid transcription factor NF-E2 (Nrf2), which critically regulates GCLC by binding to the antioxidant response elements (AREs). Vanadyl sulfate treatment increased the nuclear translocation of Nrf2 and the accumulation of phosphorylated Nrf2. Extracellular regulated kinase (ERK) contributed to ARE-driven GCLC expression via Nrf2 activation. Vanadyl sulfate induced the expression of the active phospho form of ERK. Taken together, these results suggest that the increase in GSH level by Jeju ground water is, at least in part, due to the effects of vanadyl sulfate via the Nrf2-mediated induction of GCLC.
Keywords: Jeju ground water; vanadyl sulfate; glutamate cysteine ligase; human Chang liver cells; erythroid transcription factor NF-E2
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Kim, A.D.; Zhang, R.; Kang, K.A.; You, H.J.; Hyun, J.W. Increased Glutathione Synthesis Following Nrf2 Activation by Vanadyl Sulfate in Human Chang Liver Cells. Int. J. Mol. Sci. 2011, 12, 8878-8894.
Kim AD, Zhang R, Kang KA, You HJ, Hyun JW. Increased Glutathione Synthesis Following Nrf2 Activation by Vanadyl Sulfate in Human Chang Liver Cells. International Journal of Molecular Sciences. 2011; 12(12):8878-8894.
Kim, Areum Daseul; Zhang, Rui; Kang, Kyoung Ah; You, Ho Jin; Hyun, Jin Won. 2011. "Increased Glutathione Synthesis Following Nrf2 Activation by Vanadyl Sulfate in Human Chang Liver Cells." Int. J. Mol. Sci. 12, no. 12: 8878-8894.