Effects of Exogenous Zinc on Cell Cycle, Apoptosis and Viability of MDAMB231, HepG2 and 293 T Cells

Wang, Yanhong; Li, Ke-jin; Li, Mao; Hu, Xin; Zhao, Wenjie; Hu, An; Lian, Hong-zhen; Zheng, Wei-juan

doi:10.1007/s12011-013-9737-1

Cited by 27 publications

(21 citation statements)

References 26 publications

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“…Although, the biological function of zinc transporters has not been fully elucidated, ZnT-1 expression has been reported to increase in response to increase levels of intracellular zinc [27]. This suggests that the upregulation of ZnT-1 mRNA forms part of the cellular defense system against heavy metal stress, and lends credence to our observation that ZnT-1 mRNA levels are increased by the Nrf2-ARE signal transduction pathway.…”

Section: Discussionsupporting

confidence: 71%

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

Ishida

Takechi

2016

PLoS ONE

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Zinc transporters are solute carrier family members. To date, 10 zinc transporters (ZnTs) and 14 Zrt-, Irt-like proteins (ZIPs) have been identified. ZnTs control intracellular zinc levels by effluxing zinc from the cytoplasm into the extracellular fluid, intracellular vesicles, and organelles; ZIPs also contribute to control intracellular zinc levels with influxing zinc into the cytoplasm. Recently, changes in zinc transporter expression have been observed in some stress-induced diseases, such as Alzheimer’s disease and diabetes mellitus. However, little is known regarding the mechanisms that regulate zinc transporter expression. To address this, we have investigated the effect of a well-established stress response pathway, the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) pathway, on zinc transporter mRNA levels. Exposure to 10−4 M tert-butylhydroquinone (t-BHQ), which activates Nrf2-ARE signaling, for 6 h significantly increases ZnT-1, ZnT-3, and ZnT-6 mRNAs levels, and significantly decreases ZnT-10 and ZIP-3 mRNA levels. These changes are not observed with 10−6 M t-BHQ, which does not activate Nrf2-ARE signaling. Furthermore, t-BHQ exposure does not affect metal responsive element transcription, a cis element that is activated in response to intracellular free zinc accumulation. From these results, we believe that the transcription of ZnT-1, ZnT-3, ZnT-6, ZnT-10, and ZIP-3 is influenced by the Nrf2-ARE signal transduction pathway.

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Section: Discussionsupporting

confidence: 71%

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

Ishida

Takechi

2016

PLoS ONE

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“…3) The anti leishmanial effect of zinc by inhibiting the enzymes that are important for the parasite carbohydrate metabolism and virulence [36] [37], also the increase in intracelluar zinc content of cells results in cell death, G1 and G2/M cell cycle arrest and increased apoptotic fraction [46]. All This could be enhanced by ketoconazole.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Acute Cutaneous Leishmaniasis by Oral Zinc Sulfate and Oral Ketocanazole Singly and in Combination

Sharquie¹,

Noaimi²,

Al-Salam³

2016

JCDSA

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Background: Cutaneous Leishmaniasis (CL) is an endemic disease in many countries and caused by different species of Leishmania parasite. It results in a deformed scar after a relatively long period. Many therapies have been tried in treatment of this disease. Objective: To compare the effect of oral zinc sulfate and oral ketoconazole singly and in combination in the treatment of acute cutaneous leishmaniasis. Patients and Methods: This single, blinded, therapeutic, controlled study was conducted in the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq, during the period, January 2015 to July 2015. Seventy-five patients with acute CL were enrolled in this study. The total numbers of lesions were 327, and the duration of lesions ranged from 4 to 12 (6.9 ± 0.7) weeks. The diagnosis was confirmed by smear and histopathology. Patients were divided into three groups: 24 patients in Group A were treated with oral zinc sulfate capsules 10 mg/kg/day for 6 weeks; 24 patients in Group B were treated with ketoconazole tablets 200 mg twice daily for 6 weeks and 27 patients in Group C were treated orally with a combination of zinc sulfate and ketoconazole for 6 weeks. All patients were seen regularly every 2 weeks for 6 weeks of treatment period, then monthly for the next three months as follow up period. Healing of the lesions was assessed by using Sharquie's modified Leishmania score to assess the objective response to the topical or systemic therapy. Results：After six weeks, 75 patients have completed the treatment, 24patients received zinc sulfate capsule, 24 patients received oral ketoconazole and 27 patients received a combination of both treatments. The cure rate was (60%) in the group receiving oral zinc sulfate capsuleand (50%) in the one receiving oral ketoconazole tablet (P = 0.146) and (96%) in the combination group (P ˂ 0.04). Conclusion: The combination therapy using oral zinc sulfate and oral ketoconazole gave a high cure rate. The combination therapy is a new mode of therapy as both drugs act in a synergistic way.

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“…The concentration-dependence and tissue-specificity of the response of cells to zinc stress has been extensively studied, by our own group and others, but the kinetic effects of zinc treatment on cells has received little attention [ 32 ], [ 33 ]. Moreover, most studies designed to investigate zinc homeostasis and toxicity have focused on the differential expression of a specific protein or proteome under a fixed stimulus period, such 24 or 48 h, which are the time-points that have been frequently used for 2DE analysis [ 28 – 31 ].…”

Section: Introductionmentioning

confidence: 99%

The Kinetic Response of the Proteome in A549 Cells Exposed to ZnSO4 Stress

et al. 2015

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Zinc, an essential trace element, is involved in many important physiological processes. Cell responses to zinc stress show time-dependent effects besides concentration-dependence and tissue-specificity. Herein, we investigated the time-dependent differential expression of the proteome in A549 cells after administered with ZnSO4 for both 9 and 24 h using 2DE. 123 differentially expressed protein spots were detected, most of which were up-regulated by Zn2+ treatment. Interestingly, 49 proteins exhibited significant differential expression repeatedly during these two treatment periods, and moreover showed a conserved change with different ratios and four time-dependent expression patterns. Pattern 1 (up-regulated with rapid initial induction and subsequent repression) and pattern 4 (down-regulated with steady repression) were the predominant expression patterns. The abundances of the proteins in patterns 1 and 4 after 24 h of zinc treatment are always lower than that after 9 h, indicating that exogenous zinc reduced the expression of proteins in cells after 24 h or longer. Importantly, these findings could also reflect the central challenge in detecting zinc homeostasis proteins by 2DE or other high throughput analytical methods resulting from slight variation in protein expression after certain durations of exogenous zinc treatment and/or low inherent protein content in cells. These time-dependent proteome expression patterns were further validated by measuring dynamic changes in protein content in cells and in expression of two proteins using the Bradford method and western blotting, respectively. The time-dependent changes in total zinc and free Zn2+ ion contents in cells were measured using ICP-MS and confocal microscopy, respectively. The kinetic process of zinc homeostasis regulated by muffling was further revealed. In addition, we identified 50 differentially expressed proteins which are predominantly involved in metabolic process, cellular process or developmental process, and function as binding, catalytic activity or structural molecule activity. This study further elucidates our understanding of dynamic nature of the cellular response to zinc stress and the mechanism of zinc homeostasis.

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Effects of Exogenous Zinc on Cell Cycle, Apoptosis and Viability of MDAMB231, HepG2 and 293 T Cells

Cited by 27 publications

References 26 publications

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

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

Treatment of Acute Cutaneous Leishmaniasis by Oral Zinc Sulfate and Oral Ketocanazole Singly and in Combination

The Kinetic Response of the Proteome in A549 Cells Exposed to ZnSO4 Stress

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