Cellular zinc status regulates cytomegalovirus major immediate-early promoter

Kanekiyo, Masako; Itoh, Norio; Mano, Mikiko; Kawasaki, Atsuko; Tanaka, Junji; Muto, Norio; Tanaka, Keiichi

doi:10.1016/s0166-3542(00)00108-x

Cited by 10 publications

(5 citation statements)

References 42 publications

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“…Depletion of Zn in cell culture media can be achieved by using metal ion chelators such as chelexing resins, addition of metal ion chelators such as TPEN (membrane-permeable) and DTPA (membrane-impermeable), and other metal ion chelators which are not Zn-specific such as BAPTA (1,2-bis-( o -aminophenoxy)ethane- N,N,N',N -tetra-acetic acid), EDTA (ethylenediaminetetraacetic acid) and EGTA (ethylene glycol tetraacetic acid) (Aballay et al, 1995; Frederickson et al, 2002; Hyun et al, 2001; Kanekiyo et al, 2000; Libin et al, 2002). This study focused on the chelating effects of using chelexing resin, TPEN and DTPA on the bioavailability of Zn and other important trace minerals (Mn, Fe, and Cu) on the cell culture treatment media of osteoblastic MC3T3-E1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Zn and some bone-related trace minerals are important in the study of membrane transport mechanisms and for the investigation of protein and gene expressions. At present, metal ion chelators such as chelexing resins, DTPA (diethylenetriaminepentaacetic acid), TPEN [ N,N,N',N' -tetrakis(2-pyridylmethyl) ethylenediamine], BAPTA [1,2-bis(o-aminophenoxy)ethane- N,N,N',N' -tetraacetic acid] and its derivatives, EDTA (diaminoethanetetraacetic acid) and EGTA (ethyleneglycoltetraacetic acid) are being used for limiting the available metal ions contained in cellular medium (Aballay et al, 1995; Frederickson et al, 2002; Hyun et al,2001; Kanekiyo et al, 2000; Libin et al, 2002). These metal ion chelators not only bind with the target mineral for certain studies but also bind to any possible metal ion present in the medium system.…”

Section: Introductionmentioning

confidence: 99%

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Cellular Zn depletion by metal ion chelators (TPEN, DTPA and chelex resin) and its application to osteoblastic MC3T3-E1 cells

et al. 2007

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Trace mineral studies involving metal ion chelators have been conducted in investigating the response of gene and protein expressions of certain cell lines but a few had really focused on how these metal ion chelators could affect the availability of important trace minerals such as Zn, Mn, Fe and Cu. The aim of the present study was to investigate the availability of Zn for the treatment of MC3T3-E1 osteoblast-like cells and the availability of some trace minerals in the cell culture media components after using chelexing resin in the FBS and the addition of N,N,N',N'-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN, membrane-permeable chelator) and diethylenetriaminepentaacetic acid (DTPA, membrane-impermeable chelator) in the treatment medium. Components for the preparation of cell culture medium and Zn-treated medium have been tested for Zn, Mn, Fe and Cu contents by atomic absorption spectrophotometer or inductively coupled plasma spectrophotometer. Also, the expression of bone-related genes (ALP, Runx2, PTH-R, ProCOL I, OPN and OC) was measured on the cellular Zn depletion such as chelexing or TPEN treatment. Results have shown that using the chelexing resin in FBS would significantly decrease the available Zn (p<0.05) (39.4 ± 1.5 µM vs 0.61 ± 10.15 µM) and Mn (p<0.05) (0.74 ± 0.01 µM vs 0.12 ± 0.04 µM). However, levels of Fe and Cu in FBS were not changed by chelexing FBS. The use of TPEN and DTPA as Zn-chelators did not show significant difference on the final concentration of Zn in the treatment medium (0, 3, 6, 9, 12 µM) except for in the addition of higher 15 µM ZnCl2 which showed a significant increase of Zn level in DTPA-chelated treatment medium. Results have shown that both chelators gave the same pattern for the expression of the five bone-related genes between Zn- and Zn+, and TPEN-treated experiments, compared to chelex-treated experiment, showed lower bone-related gene expression, which may imply that TPEN would be a stronger chelator than chelex resin. This study showed that TPEN would be a stronger chelator compared to DTPA or chelex resin and TPEN and chelex resin exerted cellular zinc depletion to be enough for cell study for Zn depletion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cellular Zn depletion by metal ion chelators (TPEN, DTPA and chelex resin) and its application to osteoblastic MC3T3-E1 cells

et al. 2007

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“…The role of metallothioneins remains unclear in this study; however, they have been described as negative regulators of apoptosis, albeit not through direct caspase 3 inhibition ( 37 ). Zinc and metallothioneins also facilitate human cytomegalovirus (HCMV) replication by activating the immediate-early HCMV promoter ( 38 , 39 ). Kanekiyo et al demonstrated that both zinc and metallothionein overexpression increased NF-κB binding in the HCMV promoter.…”

Section: Current Status Of Knowledgementioning

confidence: 99%

The Role of Zinc in Antiviral Immunity

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Obeid

Ahlenstiel

et al. 2019

Advances in Nutrition

619

602

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Zinc is an essential trace element that is crucial for growth, development, and the maintenance of immune function. Its influence reaches all organs and cell types, representing an integral component of approximately 10% of the human proteome, and encompassing hundreds of key enzymes and transcription factors. Zinc deficiency is strikingly common, affecting up to a quarter of the population in developing countries, but also affecting distinct populations in the developed world as a result of lifestyle, age, and disease-mediated factors. Consequently, zinc status is a critical factor that can influence antiviral immunity, particularly as zinc-deficient populations are often most at risk of acquiring viral infections such as HIV or hepatitis C virus. This review summarizes current basic science and clinical evidence examining zinc as a direct antiviral, as well as a stimulant of antiviral immunity. An abundance of evidence has accumulated over the past 50 y to demonstrate the antiviral activity of zinc against a variety of viruses, and via numerous mechanisms. The therapeutic use of zinc for viral infections such as herpes simplex virus and the common cold has stemmed from these findings; however, there remains much to be learned regarding the antiviral mechanisms and clinical benefit of zinc supplementation as a preventative and therapeutic treatment for viral infections.

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“…Indeed, with our study on the MT-null cells transfected with MT-I, MT-I expression is driven by a constitutive vector promoter, CMV, and not its native promoter (see Methods) so the increased expression after arsenic exposure in these cells would likely be indirect. The increased basal MT in MT-null cells transfected with MT-I would very likely represent a pool of potentially displaceable zinc and zinc displaced from MT has been implicated in CMV promoter-driven expression (Kanekiyo et al, 2000). …”

Section: Discussionmentioning

confidence: 99%

Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

Waalkes

2015

Toxicology and Applied Pharmacology

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We studied how the protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO2) was less cytolethal over 24 h in WT cells (LC50 = 11.0 ± 1.3 µM; mean ± SEM) than in MT-null cells (LC50 = 5.6 ± 1.2 µM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 µM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTa2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potentially sequestration of scavenging oxidant radicals and/or arsenic.

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Cellular zinc status regulates cytomegalovirus major immediate-early promoter

Cited by 10 publications

References 42 publications

Cellular Zn depletion by metal ion chelators (TPEN, DTPA and chelex resin) and its application to osteoblastic MC3T3-E1 cells

Cellular Zn depletion by metal ion chelators (TPEN, DTPA and chelex resin) and its application to osteoblastic MC3T3-E1 cells

The Role of Zinc in Antiviral Immunity

Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

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