Zinc-Induced Activation of the Human Cytomegalovirus Major Immediate-Early Promoter Is Mediated by Metallothionein and Nuclear Factor-κB

Kanekiyo, Masako; Itoh, Norio; Kawasaki, Atsuko; Tanaka, Junji; Nakanishi, Takashi; Tanaka, Keiichi

doi:10.1006/taap.2001.9173

Cited by 26 publications

(23 citation statements)

References 50 publications

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“…We and others [9,27,28,35] have described the interaction of MT with NF-κB. Abdel-Mageed and Agrawal [9] reported that MT directly interacts with NF-κB, as demonstrated by EMSA analysis.…”

Section: Discussionmentioning

confidence: 88%

“…Because of these characteristics, MT can scavenge hydroxyl radicals and donate zinc to transcription factors. We and others [9, 27,28] have reported that MT modulates NF-κB activity. Therefore we postulated that MT controls both the intracellular redox status and the zinc concentration of macrophages, and regulates these functions in immune responses.…”

Section: Introductionmentioning

confidence: 93%

“…We and others [9,27] have reported that MT up-regulates the activation of NF-κB, an essential process that precedes LPSinduced TNF-α transcription and translation. To determine …”

Section: Mt Regulates Dna Binding Activities Of Nf-κbmentioning

confidence: 99%

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Metallothionein modulates lipopolysaccharide-stimulated tumour necrosis factor expression in mouse peritoneal macrophages

Kanekiyo

Itoh

Kawasaki

et al. 2002

Biochemical Journal

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Metallothionein (MT) is a low-molecular-mass, cysteine-rich metal binding protein thought to be involved in the detoxification of heavy metals and scavenging of free radicals. MT is directly induced not only by heavy metals, but also by hormones and cytokines. The present study, which uses mice with genetic deletions of the MT proteins (MT −/− mice), was designed to evaluate the effects of MT on the expression of pro-inflammatory cytokines in macrophages. We found that the production of tumour necrosis factor (TNF) induced by lipopolysaccharide (LPS) in peritoneal macrophages is up-regulated by MT via the modulation of nuclear factor κB (NF-κB) activity. This conclusion is supported by the following observations : (1) LPS stimulated the secretion of less TNF activity from MT −/−

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 93%

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Metallothionein modulates lipopolysaccharide-stimulated tumour necrosis factor expression in mouse peritoneal macrophages

Kanekiyo

Itoh

Kawasaki

et al. 2002

Biochemical Journal

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“…For MT stable expression, Chinese Hamster Lung (CHL) cells were transfected with pBPVGRPMT or pBPVGRPTM by the calcium phosphate precipitation method as previously described. 19) After G418 selection and cloning, the presence of the transgene was detected by PCR. The concentration of MT was determined using the 109 Cd/hemoglobin affinity assay.…”

Section: Methodsmentioning

confidence: 99%

Metal Response Element-binding Transcription Factor-1 Is Activated by Degradation of Metallothionein

Kimura

Okumura

Oguro

et al. 2009

JOURNAL OF HEALTH SCIENCE

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Cytosolic zinc-binding protein, metallothionein (MT), is normally saturated with Zn. It is thought that Znsaturated MT (Zn-MT) acts as a major intracellular Zn pool. Metal-response element-binding transcription factor-1 (MTF-1) plays an important role in Zn-mediated MT transcription. Here, we showed that degradation of Zn-MT activates MTF-1. We measured activated MTF-1 using an electrophoretic mobility shift assay. Interleukin-6 induced MT expression and increased MTF-1 activity. MTF-1 activation was not observed in MT-overexpressing cells. MT-dependent MTF-1 activation was observed only after treating MT-overexpressing cells with cycloheximide (CHX), a protein synthesis inhibitor. CHX-treatment increased the degradation/synthesis ratio of protein. An increase in the degradation/synthesis ratio for the MT protein is expected to increase the level of labile Zn and activate MTF-1. Recombinant MTF-1 was activated by H 2 O 2 only in the presence of Zn-MT. Oxidative stress activated MTF-1 DNA-binding activity in primary cultured hepatocytes but not in MT-deficient hepatocytes. These findings suggest that degradation of Zn-MT activates MTF-1, and that MT plays an important role in zinc-mediated signal transduction.

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“…2). 70,71) Activity of the human cytomegalovirus major immediate-early promoter was regulated by intracellular zinc levels. Overexpression of MT upregulates the DNA binding of NF-κB and thus NF-κB-induced activation MTF-1 activation during endotoxemia is mediated by an increase in Zn-MT.…”

Section: Function Of Mt In Modification Of Transcriptional Activitymentioning

confidence: 99%

Function of Metallothionein in Gene Expression and Signal Transduction: Newly Found Protective Role of Metallothionein

Kimura

Itoh

2008

JOURNAL OF HEALTH SCIENCE

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A heavy-metal-binding protein, metallothionein (MT), is induced by heavy metal overload and reactive oxygen species (ROS). The metals and ROS are rendered harmless by binding to MT or by oxidizing MT, respectively. This is a well-known role of MT. MT is also induced by glucocorticoids and cytokines. Induced MT may increase intracellular free zinc and modulate the activity of transcription factors. Changes in MT levels are thought to help in adaptation to changes in environmental conditions. MT modulates inflammatory reactions, including lipopolysaccharide (LPS)-induced expression of cytokines, nitric oxide production from macrophages in response to LPS, and resistance to LPS/D-galactosamine-induced lethality. In this review, we focus on a newly found protective role of MT, which acts mainly via changes in intracellular zinc levels or modulation of gene expression.

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Zinc-Induced Activation of the Human Cytomegalovirus Major Immediate-Early Promoter Is Mediated by Metallothionein and Nuclear Factor-κB

Cited by 26 publications

References 50 publications

Metallothionein modulates lipopolysaccharide-stimulated tumour necrosis factor expression in mouse peritoneal macrophages

Metallothionein modulates lipopolysaccharide-stimulated tumour necrosis factor expression in mouse peritoneal macrophages

Metal Response Element-binding Transcription Factor-1 Is Activated by Degradation of Metallothionein

Function of Metallothionein in Gene Expression and Signal Transduction: Newly Found Protective Role of Metallothionein

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