Clinical significance of metallothioneins in cell therapy and nanomedicine

Sharma, Sushil; Rais, Afsha; Sandhu, Ranbir S.; Nel, Wynand; Ebadi, Manuchair

doi:10.2147/ijn.s42019

Cited by 52 publications

(33 citation statements)

References 79 publications

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“…MTs are capable of self-protection through maintenance of copper and zinc levels and they also directly protect against ROS (Shiraga et al, 1993). Recently, MTs were shown to inhibit the formation of inclusion body-like structures, Charnoly bodies, mitochondrially formed electron-dense membrane stacks found in neurons, leading to a lower observed incidence of alpha-synucleinopathies (Sharma et al, 2013b; Sharma and Ebadi, 2014a,b). The scavenging ability of MTs to combat ROS leads to a lowering of oxidative stress and therefore a potential role in neuroprotection against PD (Ebadi et al, 2005; Ebadi and Sharma, 2006; Hozumi, 2013).…”

Section: Oxidative Stress and Neuroinflammationmentioning

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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Section: Oxidative Stress and Neuroinflammationmentioning

confidence: 99%

Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies

et al. 2017

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“…1). Moreover, there is increasing number of papers aimed at describing the role of these proteins in anticancer therapy [5][6][7][8][9][10].…”

Section: Metallothioneinsmentioning

confidence: 99%

Microarray analysis of metallothioneins in human diseases—A review

Křížková

Kępińska

Emri

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Microarray analysis of metallothioneins in human diseases AbstractMetallothioneins (MTs), low molecular mass cysteine-rich proteins, which are able to bind up to 20 monovalent and up to 7 divalent heavy metal ions are widely studied due to their functions in detoxification of metals, scavenging free radicals and cells protection against the oxidative stress. It was found that the loss of the protective effects of MT leads to an escalation of pathogenic processes and carcinogenesis. 3The most extensive area is MTs expression for oncological applications, where the information about gene patterns is helpful for the identification biological function, resistance to drugs and creating the correct chemotherapy. In other medical applications the effect of oxidative stress to cell lines exposed to heavy metals and hydrogen peroxide is studied as well as influence of drugs and cytokines on MTs expression and MTs expression in the adiposetissue. The precise detection of low metallothionein concentrations and its isoforms is necessary to understand the connection between quantity and isoforms of MTs to size, localization and type of cancer. This information is necessary for well-timed therapy and increase the chance to survival. Microarray chips appear as good possibility for finding all information about expression of MTs genes and isoforms not only in cancer, but also in other diseases, especially diabetes, obesity, cardiovascular diseases, ageing, osteoporosis, psychiatric disorders and as the effects of toxic drugs and pollutants, which is discussed in this review. List of abbreviations:HCC -hepatocellular carcinoma, HFD -high fat diet, MMP -matrix metalloproteinase, MT -metallothionein, MTF -metal transcription factor, MRE -metal responsive element, ROS -reactive oxygen species.

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“…Первичная структура представлена 60 аминокислотами, из которых одна треть -это аминокислотные остатки цистеина [9].…”

Section: Sh-содержащие соединенияunclassified