Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells

Ishida, Tatsuro; Takechi, Seiji

doi:10.1371/journal.pone.0166100

Cited by 15 publications

(13 citation statements)

References 34 publications

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“…Increasing evidence shows an effect of zinc on diabetic complications, seemingly through Nrf2. It is demonstrated that the Nrf2-ARE signal transduction pathway increases ZnT-1, ZnT-3, and ZnT-6 mRNA levels, and decreases ZnT-10 and ZIP-3 mRNA levels [ 20 ]. In this study, Nrf2 mRNA expression was found to be significantly decreased in the blood of patients with DN.…”

Section: Discussionmentioning

confidence: 99%

Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy

et al. 2022

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Objective We investigated the correlation between zinc levels and Nrf2 expression and potential effects on the clinicopathology of patients with diabetic nephropathy (DN). Methods We selected 30 patients with DN, diagnosed via renal biopsy at our hospital from March 2018 to November 2019, and enrolled 30 healthy individuals from a medical examination center as the control group. Patients with DN were divided into normal-zinc and low-zinc groups. We detected the levels of zinc, copper, and Nrf2 mRNA in their serum, and collected the clinical and pathological data of DN patients. Results Serum zinc level and Nrf2 mRNA expression were significantly decreased in patients with DN compared to those of healthy people (P < 0.05). Of the 30 patients, 16 had low zinc (53.3%) and 14 had normal zinc levels (46.7%). There was no significant difference in the blood Nrf2 mRNA expression between the two groups (P > 0.05). However, the expression of Nrf2 in the kidney tissue of the low-zinc group was significantly lower compared to the normal-zinc group (P < 0.05). Diastolic blood pressure and copper levels were significantly higher in the low-zinc group (P < 0.05). In contrast, body mass index, red blood cell count, Hb level, and the ratio of zinc to copper were significantly lower in the low-zinc group (P < 0.05). The pathological classifications of the low-zinc group were more severe (P < 0.05). Conclusion Patients with DN were more likely to have zinc deficiency and lower expression of Nrf2. Additionally, DN patients with zinc deficiency were prone to have more severe clinical and pathological manifestations.

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Section: Discussionmentioning

confidence: 99%

Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy

et al. 2022

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“…We have previously discussed zinc and citrate-mediated switching between glycolysis and TCA during PCa progression. NRF2 activation increases expression of zinc transporters (Ishida and Takechi, 2016), which efflux zinc from the intracellular organelles (such as mitochondria) and inhibits its reuptake. Therefore, higher NRF2 levels in advanced PCa help to keep zinc levels low inside the cells and in the mitochondria (Ishida and Takechi, 2016), which enhances the TCA cycle.…”

Section: Nrf2 In Metabolic Changes In Pcamentioning

confidence: 99%

NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression

et al. 2022

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Metabolic alterations are a common survival mechanism for prostate cancer progression and therapy resistance. Oxidative stress in the cellular and tumor microenvironment dictates metabolic switching in the cancer cells to adopt, prosper and escape therapeutic stress. Therefore, regulation of oxidative stress in tumor cells and in the tumor-microenvironment may enhance the action of conventional anticancer therapies. NRF2 is the master regulator for oxidative stress management. However, the overall oxidative stress varies with PCa clinical stage, metabolic state and therapy used for the cancer. In agreement, the blanket use of NRF2 inducers or inhibitors along with anticancer therapies cause adverse effects in some preclinical cancer models. In this review, we have summarized the levels of oxidative stress, metabolic preferences and NRF2 activity in the different stages of prostate cancer. We also propose condition specific ways to use NRF2 inducers or inhibitors along with conventional prostate cancer therapies. The significance of this review is not only to provide a detailed understanding of the mechanism of action of NRF2 to regulate oxidative stress-mediated metabolic switching by prostate cancer cells to escape the radiation, chemo, or hormonal therapies, and to grow aggressively, but also to provide a potential therapeutic method to control aggressive prostate cancer growth by stage specific proper use of NRF2 regulators.

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“…The RNA extraction and qRT-PCR were carried out according to the procedures reported previously (Ishida and Takechi, 2016). Briefly, total RNA was extracted from HepG2 cells using the RNeasy ® Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions.…”

Section: Rna Extraction and Quantitative Real-time Polymerase Chain Rmentioning

confidence: 99%

“…The qRT-PCR assays were performed on a StepOnePlus™ real-time PCR system (Thermo Fisher Scientific) using THUNDERBIRD ® SYBR ® qPCR Mix (Toyobo) and melting curve analysis. The primer sequences and estimated product sizes have been described previously (Ishida and Takechi, 2016). The Ct value was calculated using StepOnePlus™ software.…”

Section: Rna Extraction and Quantitative Real-time Polymerase Chain Rmentioning

confidence: 99%

β-Naphthoflavone, an exogenous ligand of aryl hydrocarbon receptor, disrupts zinc homeostasis in human hepatoma HepG2 cells

Ishida

Takechi

2019

J. Toxicol. Sci.

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Recent studies have demonstrated a relationship between the disruption of zinc homeostasis and the onset of diseases. However, little is known about the factors that disrupt zinc homeostasis. Here, we investigated the effects of β-naphthoflavone, an exogenous ligand of aryl hydrocarbon receptor (AHR), on intracellular zinc levels. Human hepatoma HepG2 cells were treated with β-naphthoflavone for 3 days, and intracellular labile and total zinc levels were assessed through flow cytometry and inductively coupled plasma atom emission spectroscopy, respectively. The mRNA levels of zinc transporters were determined by real-time PCR. Treatment of cells with β-naphthoflavone induced a decrease in intracellular labile zinc in a dose-dependent manner, with significantly decreased levels observed at 1 µM compared with controls. Additionally, intracellular total zinc levels demonstrated a decreasing trend with 10 µM β-naphthoflavone. Zinc pyrithione recovered the decrease in intracellular labile zinc levels induced by β-naphthoflavone, while zinc sulfate had no effect. Moreover, significant decreases in the mRNA levels of zinc transporters ZnT10 and ZIP5 were observed in response to 10 µM β-naphthoflavone. These results demonstrated that β-naphthoflavone has the potential to disrupt zinc homeostasis in hepatocytes. Although the underlying mechanism remains to be determined, suppression of zinc transporter transcription through AHR activation may be involved in the β-naphthoflavone-induced disruption of intracellular zinc levels.

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Nrf2-ARE-Dependent Alterations in Zinc Transporter mRNA Expression in HepG2 Cells

Cited by 15 publications

References 34 publications

Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy

Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy

NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression

β-Naphthoflavone, an exogenous ligand of aryl hydrocarbon receptor, disrupts zinc homeostasis in human hepatoma HepG2 cells

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