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

Kimura, Toshikiro; Itoh, Norio

doi:10.1248/jhs.54.251

Cited by 28 publications

(24 citation statements)

References 89 publications

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“…Several studies have shown that metals such as copper, zinc, and mercury are important inducers of MT synthesis, especially between 6 and 48 h after exposure [38][39][40][41][42][43]. Thus, we believe that the lower Hg content from animals that received Zn-Hg may be related to the synthesis of MT, since these proteins are rich in SH groups that may sequester Hg ions helping in its elimination.…”

Section: Discussionmentioning

confidence: 89%

Zinc and N-acetylcysteine modify mercury distribution and promote increase in hepatic metallothionein levels

Oliveira

Mesquita

et al. 2015

Journal of Trace Elements in Medicine and Biology

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Section: Discussionmentioning

confidence: 89%

Zinc and N-acetylcysteine modify mercury distribution and promote increase in hepatic metallothionein levels

Oliveira

Mesquita

et al. 2015

Journal of Trace Elements in Medicine and Biology

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“…MT-3 differs by a unique acidic insert comprised of six amino acids and two Pro substitutions and has an observed ability to inhibit cell growth in cultured neurons (Palmiter et al, 1992; Chung et al, 2003; Howells et al, 2010). Recent work showed MT to be neuroprotective against proteinopathies in neurodegenerative disease, a finding which is reinforced by low MT-3 levels in neurons of Alzheimer's patients compared to healthy individuals (Kimura and Itoh, 2008; Howells et al, 2010; Uchida, 2010). Interestingly, this same deficiency is seen in PD, although this finding may be somewhat controversial (Hozumi et al, 2004).…”

Section: Metallothioneinsmentioning

confidence: 99%

Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies

et al. 2017

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Metallothioneins (MTs) are proteins that function by metal exchange to regulate the bioavailability of metals, such as zinc and copper. Copper functions in the brain to regulate mitochondria, neurotransmitter production, and cell signaling. Inappropriate copper binding can result in loss of protein function and Cu(I)/(II) redox cycling can generate reactive oxygen species. Copper accumulates in the brain with aging and has been shown to bind alpha-synuclein and initiate its aggregation, the primary aetiological factor in Parkinson's disease (PD), and other alpha-synucleinopathies. In PD, total tissue copper is decreased, including neuromelanin-bound copper and there is a reduction in copper transporter CTR-1. Conversely cerebrospinal fluid (CSF) copper is increased. MT-1/2 expression is increased in activated astrocytes in alpha-synucleinopathies, yet expression of the neuronal MT-3 isoform may be reduced. MTs have been implicated in inflammatory states to perform one-way exchange of copper, releasing free zinc and recent studies have found copper bound to alpha-synuclein is transferred to the MT-3 isoform in vitro and MT-3 is found bound to pathological alpha-synuclein aggregates in the alpha-synucleinopathy, multiple systems atrophy. Moreover, both MT and alpha-synuclein can be released and taken up by neural cells via specific receptors and so may interact both intra- and extra-cellularly. Here, we critically review the role of MTs in copper dyshomeostasis and alpha-synuclein aggregation, and their potential as biomarkers and therapeutic targets.

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“…They are involved in transporting and detoxifying of metal ions [2,3]. On the basis of recently published papers, their role in carcinogenesis can be considered [4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Using of chicken antibodies for metallothionein detection in human blood serum and cadmium‐treated tumour cell lines after dot‐ and electroblotting

et al. 2009

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Metallothionein (MT) is a low-molecular mass protein playing an essential role in homeostasis of heavy metal ions. Its relation with formation and progression of a tumour disease is discussed in this article. Here, we propose a new methodological approach for visualization of MT on PVDF membranes after dot- and electroblotting by using a commercial mouse monoclonal antibody E9 and polyclonal chicken antibodies. The optimized procedure was as follows. We dotted 1 microL sample volume on PVDF membrane and let it to dry. Then, we blocked the membrane surface with 2% BSA in PBS for 30 min. After that, the membrane was incubated in chicken primary antibody (diluted 1:500), washed, and incubated in rabbit-anti-chicken secondary antibody conjugated with horseradish peroxidase. To visualize the interaction, we used 3-aminoethyl-9-carbazole. Under these conditions, we estimated detection limit as 3 pg of MT per 1 microL. The optimal approach was further utilized for detection of MT level in two human fibroblast cell lines and in blood serum obtained from children with medulloblastoma. The results were in good agreement with differential pulse voltammetry-Brdicka reaction.

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

Cited by 28 publications

References 89 publications

Zinc and N-acetylcysteine modify mercury distribution and promote increase in hepatic metallothionein levels

Zinc and N-acetylcysteine modify mercury distribution and promote increase in hepatic metallothionein levels

Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies

Using of chicken antibodies for metallothionein detection in human blood serum and cadmium‐treated tumour cell lines after dot‐ and electroblotting

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