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Metallothionein (MT) structure. Model of two binding sites of metallothionein. Red big beads are metal atoms (e.g., Zn), and small yellow beads are sulfur atoms. Adopted and modified according to [27]. 

Metallothionein (MT) structure. Model of two binding sites of metallothionein. Red big beads are metal atoms (e.g., Zn), and small yellow beads are sulfur atoms. Adopted and modified according to [27]. 

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Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can be either beneficial or harmful for living systems. It is clear that there are numerous mechanis...

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... these low molecular weight cysteine-rich proteins have been continuously studied in all aspects, including physical, chemical and biochemical properties. Mammalian MTs may contain 61–68 amino acids, and among them 20 are cysteines [16,17]. These unique proteins are involved in diverse intracellular functions [18], but their role in the detoxification of heavy metals and in the maintaining of essential metal ion homeostasis, which is due to their high affinity for these metals, is mostly investigated [19,20]. For mammals, MTs bind zinc [21], but with excess copper or cadmium, zinc can be easily replaced by these metals [22]. Cells that contain excessive amounts of MTs are resistant to cadmium toxicity [23], while cell lines that cannot synthesize MTs are sensitive to cadmium [24]. Genetic studies using transgenic or knockout mouse models are further evidence of the role of MTs in protection against cadmium toxicity [25,26]. Based on structural models, it can be assumed that the MT molecule is composed of two binding domains, α and β , which are composed of cysteine clusters. Covalent binding of metal atoms involves sulfhydryl cysteine residues ( Figure 1). The N -terminal part of the peptide is designated as β -domain and has three binding sites for divalent ions, and the C-terminal part (the α -domain) has the ability to bind four divalent metal ions. Four mammalian MT isoforms (MT-1–MT-4) and 13 MT-like human proteins were identified [28]. The differences of constituent forms come mainly from post-translational modifications, small changes in primary structure, type of incorporated metal ion and speed of degradation. Despite the physical-chemical similarity of the forms, their roles and occurrence in tissues vary significantly [29]. MT-1 and MT-2 are present almost in all types of soft tissues [30–32], MT-3 is expressed mostly in brain tissue, but also in heart, kidneys and reproductive organs [33,34] and the MT-4 gene was detected in stratified squamous epithelial cells associated with oral epithelia, esophagus, upper stomach, tail, footpads and neonatal skin. [35]. In humans, the MT genes are located on chromosome 16 in a cluster and involve 16 identified genes, from which five are pseudogenes [36]. Although the MT-II, MT-III and MT-IV proteins are encoded by a single gene, the MT-I protein comprises ...
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... on structural models, it can be assumed that the MT molecule is composed of two binding domains, α and β, which are composed of cysteine clusters. Covalent binding of metal atoms involves sulfhydryl cysteine residues (Figure 1). The N-terminal part of the peptide is designated as β-domain and has three binding sites for divalent ions, and the C-terminal part (the α-domain) has the ability to bind four divalent metal ions. ...

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... Metallothioneins are a family of small (~6 kDa) proteins containing stretches of 20 cysteine residues, which allow them to bind ions of heavy metals (gold, silver, cadmium, etc.) [54,55]. Metallothioneins have been found in different organisms [56]; they are involved in protection against the toxic effects of heavy metal salts [57] and oxidative stress [58]. ...
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... It is known that their reactivity can be significantly changed in the presence of vitamins C and E [36]. Selenium compounds can reduce peroxides and have a great influence on the release of zinc by metallothionein [22,34,37]. However, the lowest OS value was calculated for the sample with BiVits® ACTIVA Recovery, which possesses the strongest antioxidant effect. ...
... In addition, due to their high thiol content, these proteins were involved in quenching hydroxyl (OH . ) and superoxide radicals (O 2 -. ) [107]. Under our experimental conditions, the significant increase of MT levels in PEN-exposed clams reflected probably an adaptive approach adopted by R. decussates to reduce this fungicide. ...
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... Consistent with this difference, we demonstrated that all brake-wear PM types could upregulate the expression of genes encoding metallothioneins, cysteine-rich metal-chelating proteins [49]. Metallothioneins are canonically described as zinc-binding proteins [50], which play an important role in regulating the intracellular free concentration of zinc [49]. When intracellular free zinc concentrations increase, zinc binds to metal regulatory transcription factor 1 (MTF1), promoting nuclear translocation and binding to and Oxidative Stress Score. ...
... In C and D, a Pearson's correlation was used. In F and G, and two-tailed paired t-test was used promoter sequences on metallothionein genes, increasing their expression to maintain zinc homeostasis [49]. In this context, it is notable that SemiMxCu-derived brakewear PM contained more zinc than any of the other vehicle-derived PM types examined, however, NAO and ceramic brake-wear PM still induced the highest magnitude response in metallothionein gene expression. ...
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... For instance, z plays a key role in antioxidant defense systems, DNA repair, and enzyme functio However, Cd disrupts Zn homeostasis in astrocytes by competing with Zn for sites, thereby displacing Zn and perturbing its normal functions [204,205]. This eve weakens the antioxidant defense of glial cells and causes CNS disease susceptibilit Also, considering that Zn is responsible for the functioning of metallothioneins (a that catalyzes the detoxification of metals against oxidative stress), the Cd-indu homeostasis imbalance can further lead to uncontrolled cellular damage that is imp in many neurodegenerative diseases [207,208]. ...
... This eventually weakens the antioxidant defense of glial cells and causes CNS disease susceptibility [206]. Also, considering that Zn is responsible for the functioning of metallothioneins (a protein that catalyzes the detoxification of metals against oxidative stress), the Cd-induced Zn homeostasis imbalance can further lead to uncontrolled cellular damage that is implicated in many neurodegenerative diseases [207,208]. ...
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... For instance, z plays a key role in antioxidant defense systems, DNA repair, and enzyme functio However, Cd disrupts Zn homeostasis in astrocytes by competing with Zn for sites, thereby displacing Zn and perturbing its normal functions [204,205]. This eve weakens the antioxidant defense of glial cells and causes CNS disease susceptibilit Also, considering that Zn is responsible for the functioning of metallothioneins (a that catalyzes the detoxification of metals against oxidative stress), the Cd-indu homeostasis imbalance can further lead to uncontrolled cellular damage that is imp in many neurodegenerative diseases [207,208]. ...
... This eventually weakens the antioxidant defense of glial cells and causes CNS disease susceptibility [206]. Also, considering that Zn is responsible for the functioning of metallothioneins (a protein that catalyzes the detoxification of metals against oxidative stress), the Cd-induced Zn homeostasis imbalance can further lead to uncontrolled cellular damage that is implicated in many neurodegenerative diseases [207,208]. ...
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... Scavenging ROS with NAC abolished the shMT2A selectivity of encorafenib and reduced cell loss ( Figure 7C). zinc-finger transcription factors [32], mobilization of zinc [33], and contributing to the redox cycle of glutathione [34], the primary cytoplasmic antioxidant. ROS signals through the BRAF/CRAF-MEK-MAPK pathway, often upstream of RAF through RAS activation [35]. ...
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... These results are consistent with previous studies which showed that metallothionine proteins are involved in oxidative stress and inhibition of metallothionine proteins can increase cancer cell growth by regulating zinc-finger proteins. [25,26] To validate the RNA-seq results, we performed a subsequent RT-qPCR study in BxPC3 cells treated with DMSO, PK9328, or MS172 at different concentrations (Figure 5e). We observed a concentration-dependent upregulation of MT1X and MT1N genes and a simultaneous downregulation of ZNF391 and ZNF778 genes at 4 h time point induced by MS172, while PK9328 treatment led to no changes compared to the DMSO control. ...
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