Balance between metallothionein and metal response element binding transcription factor 1 is mediated by zinc ions (Review)

Dong, Gang; Chen, Hong; Qi, Mei-Yu; Yu, Dou; Wang, Qinglu

doi:10.3892/mmr.2014.2969

Cited by 50 publications

(33 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MTs, are small (6–7 KDa) native Zn/Cd binding proteins (Margoshes and Vallee, 1957; Kägi and Vallee, 1960), composed of cysteine-metal cores that have a high affinity for copper (Pountney et al, 1995; Nordberg, 1998; Hozumi et al, 2004; Carpenè et al, 2007; Dong et al, 2015). MT-knockout mice become extremely susceptible to the effects of environmental stress, including copper-exposure (West et al, 2008; Manso et al, 2011; Petro et al, 2016).…”

Section: Metallothioneinsmentioning

confidence: 99%

Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

Section: Metallothioneinsmentioning

confidence: 99%

Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies

et al. 2017

View full text Add to dashboard Cite

show abstract

“…“Free” metal ions can lead to harmful side reactions, or can be scavenged by pathogens [28,29]. MTs are part of a complex network of proteins, metallochaperones, that are involved in the transport and storage of essential metals and maintenance of metal homeostasis [30,31]. MT has been shown to directly donate zinc to metallo-enzymes like carbonic anhydrase [32] and drive copper to cellular locales by a binding affinity gradient [33].…”

Section: Metallothioneinmentioning

confidence: 99%

Residue Modification and Mass Spectrometry for the Investigation of Structural and Metalation Properties of Metallothionein and Cysteine-Rich Proteins

Irvine

Stillman

2017

IJMS

View full text Add to dashboard Cite

Structural information regarding metallothioneins (MTs) has been hard to come by due to its highly dynamic nature in the absence of metal-thiolate cluster formation and crystallization difficulties. Thus, typical spectroscopic methods for structural determination are limited in their usefulness when applied to MTs. Mass spectrometric methods have revolutionized our understanding of protein dynamics, structure, and folding. Recently, advances have been made in residue modification mass spectrometry in order to probe the hard-to-characterize structure of apo- and partially metalated MTs. By using different cysteine specific alkylation reagents, time dependent electrospray ionization mass spectrometry (ESI-MS), and step-wise “snapshot” ESI-MS, we are beginning to understand the dynamics of the conformers of apo-MT and related species. In this review we highlight recent papers that use these and similar techniques for structure elucidation and attempt to explain in a concise manner the data interpretations of these complex methods. We expect increasing resolution in our picture of the structural conformations of metal-free MTs as these techniques are more widely adopted and combined with other promising tools for structural elucidation.

show abstract

“…As it was shown, MT concentration can be significantly increased in Nile tilapia ( Oreochromis niloticus L.), common carp ( Cyprinus carpio L.) and abalone ( Haliotis diversicolor ) when exposed to Cd (Abdel‐Tawwab & Wafeek, ; Huang et al, ; Huang, Zhang, Chen, Zhuang, & Wang, ). In response to heavy metal ions or oxidative stress, metal‐responsive transcription factor‐1 (MTF‐1), which is the most comprehensively studied as an upstream regulatory element of MT, is also involved in the mediation of intracellular metal ion balance (Dong, Chen, Qi, Dou, & Wang, ; Günther, Davis, Georgiev, & Schaffner, ). Additionally, MTF‐1 was also found to be Cd inducible in Haliotis discus hannai (Lee & Nam, ).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of dietary α-lipoic acid on abalone Haliotis discus hannai against the oxidative damage under waterborne cadmium stress

Huang

Lei

et al. 2018

Aquacult Nutr

View full text Add to dashboard Cite

A 60‐day feeding trial was conducted to investigate the protective effects of dietary α‐lipoic acid (LA) on juvenile abalone Haliotis discus hannai against the oxidative damage under waterborne cadmium (Cd) stress. Three experimental diets were formulated with 0 (Control), 700 (LA‐700) and 2100 (LA‐2100) mg/kg supplement of LA respectively. Each diet was randomly assigned to three replicates of 50 abalones (initial body weight: 3.17 ± 0.01 g), which were exposed to 0.35 mg/L of waterborne Cd. Results showed that abalones’ Cd bioaccumulation in the serum, mantle, gill, muscle and hepatopancreas were significantly reduced in LA supplement groups. Besides, in hepatopancreas, the activities of antioxidative enzymes and concentration of glutathione (GSH) in LA supplement group were significantly higher than those in control. Meanwhile, in hepatopancreas, LA‐2100 group showed a significantly decreased malondialdehyde (MDA) concentration and the protein carbonyls in LA supplement groups were significantly lower than those in control. Diets with LA supplementation significantly upregulated the mRNA expression of HdhMTF‐1 (H. discus hannai metal‐responsive transcription factor‐1) and HdhMT (H. discus hannai metallothionein), and elevated metallothionein (MT) concentrations in hepatopancreas. In conclusion, it was suggested that dietary LA could alleviate Cd‐induced oxidative damage through enhancing antioxidative enzyme activities and upregulating the HdhMTF‐1‐mediated HdhMT transcription and synthesis.

show abstract

Balance between metallothionein and metal response element binding transcription factor 1 is mediated by zinc ions (Review)

Cited by 50 publications

References 41 publications

Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies

Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies

Residue Modification and Mass Spectrometry for the Investigation of Structural and Metalation Properties of Metallothionein and Cysteine-Rich Proteins

Protective effects of dietary α-lipoic acid on abalone Haliotis discus hannai against the oxidative damage under waterborne cadmium stress

Contact Info

Product

Resources

About