Reduced zinc cytotoxicity following differentiation of neural stem/progenitor cells into neurons and glial cells is associated with upregulation of metallothioneins

Nishikawa, Mayu; Mori, Hideki; Hara, Masayuki

doi:10.1016/j.etap.2015.04.009

Cited by 8 publications

(4 citation statements)

References 24 publications

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“…14 Nishikawa et al have found that zinc increases the viability up to 100 µmol/l, which is higher than the maximum zinc ion release for 10% Zn-PCL. 13 Also they have found that toxicity in immature neural stem/progenitor cells was decreased after differentiation into neurons and glial cells by upregulation of MTs. It can be concluded that the increase in zinc chloride concentration causes an increased proliferation and attachment as well as differentiation of the mesenchymal stem cells.…”

Section: Resultsmentioning

confidence: 99%

“…11,12 Zinc (Zn) is a vital trace element found in different body tissues, such as brain, liver, and bone. 13 It is essential for the proper protein functioning including transcription factors and enzymes needed for DNA replication and cellular proliferation, 14,15 Zinc deficiency causes abnormalities in nervous, endocrine, and immune system functions, 16 so regulation of zinc metabolism in a whole body level is important. Zinc-dependent enzymes, such as metalloproteinases and zinc-binding proteins, such as metallothioneins (MTs) have a function in the metabolism and zinc signaling by regulating its intracellular level.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced mesenchymal stem cells growth on antibacterial microgrooved electrospun zinc chloride/polycaprolactone conduits for peripheral nerve regeneration

Ekram

El‐Hady

El-Kady

et al. 2021

Journal of Bioactive and Compatible Polymers

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In this study, we have investigated the effect of adding zinc chloride (ZnCl2) on polycaprolactone (PCL) before and after electrospinning. The rheological properties and conductivity of ZnCl2/PCL solutions were measured prior to the electrospinning process. The resultant electrospun mats were characterized by SEM, contact angle, FTIR, XRD, mechanical properties, as well as its antibacterial and stem cell proliferation assessment were tested. It was found that the fibers became finer by increasing the zinc salt content. Moreover, stability increased slightly up to 5% Zn-PCL and also the hydrophilicity has been enhanced by 52%. By adding ZnCl2, the degradation rate and mechanical properties were significantly increased. Also, the resultant mats have shown antibacterial properties against S. aureus than E. coli. From the stem cells proliferation study, it can be observed that by increasing ZnCl2, the stem cells proliferation was significantly increased. Grooved multichannel nerve conduits were successfully fabricated by rolling the electrospun mats produced on corn husks which has shown better cell alignment and attachment. Hence, adding zinc chloride is a facile biocompatible enhancement to polycaprolactone nanofibers to be used in nerve regeneration.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced mesenchymal stem cells growth on antibacterial microgrooved electrospun zinc chloride/polycaprolactone conduits for peripheral nerve regeneration

Ekram

El‐Hady

El-Kady

et al. 2021

Journal of Bioactive and Compatible Polymers

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“…We recently reported the cytotoxicity of Zn 2+ ion against NSPCs and their differentiated cells in vitro (Nishikawa et al, 2015). In this study, the IC 50 values of CdCl 2 , ZnCl 2 , and…”

Section: Discussionmentioning

confidence: 73%

Effects of subcytotoxic cadmium on morphology of glial fibrillary acidic protein network in astrocytes derived from murine neural stem/progenitor cells

Mori

Sasaki

Nishikawa

et al. 2015

Environmental Toxicology and Pharmacology

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The susceptibility of mouse neural stem/progenitor cells (NSPCs) to heavy-metal cytotoxicity was assessed by measuring cell viability following exposure to heavy metal chlorides (ZnCl2, CdCl2, CuCl2, and HgCl2, respectively). We determined half-maximal inhibitory concentration (IC50) values, subcytotoxic doses, capacity for neural differentiation, and morphological features of glial fibrillary acidic protein (GFAP) network at the subcytotoxic doses of heavy metal ions. Experiments were performed using two protocols for the exposure at subcytotoxic doses of heavy metal ions; these protocols included simultaneous exposure with the induction of NSPC differentiation and sequential exposure after the induction for 1 week. Exposure to HgCl2 using both protocols reduced the ratio of neuronal NSPC differentiation. Although sequential exposure to CdCl2 reduced the size of GFAP network, simultaneous exposure did not induce any change. In conclusion, image analyses of the cytoskeletal morphology of NSPCs as a novel tool for assessing neurodevelopmental cytotoxicity enabled us to obtain new information about the localization of cytoskeletal proteins.

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“…Moreover, stable exogenous MT1G overexpression favored goblet and blunted enterocyte differentiation in both models. Previous studies have shown MTs to be upregulated in vitro upon CRC differentiation (25), and demonstrated a role for MTs in modulating differentiation in different tissues, such as human salivary gland tumor cells (where MT1F overexpression resulted in slower growing and more differentiated tumors) (26), leukemic (27) neurons and glial (28), and T cells (29). However, to the best of our knowledge, this is the first study showing a direct functional involvement of a metallothionein isoform in CRC differentiation.…”

Section: Discussionmentioning

confidence: 99%

Metallothionein 1G promotes the differentiation of HT-29 human colorectal cancer cells

Bravo¹,

Mordoh

Bianchini

2017

Oncology Reports

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Metallothioneins (MTs) are a family of low- molecular-weight, cysteine-rich proteins involved in zinc and redox metabolism, that are epigenetically downregulated during colorectal cancer (CRC) progression, but may be re-induced with a variety of agents. Since loss of MT expression is associated with a worse prognosis, in the present study we investigated the effects of overexpression of the most significantly downregulated isoform in CRC, namely MT1G, on the HT-29 cell line. Overexpression of MT1G resulted in xenograft tumors with an aberrant morphology, characterized by an evident increase in mucin-containing cells that were identified as goblet cells under electron microscopy. Immunohistochemical detection of CDX2 and cytokeratin 20 was also increased, as were goblet-cell and enterocyte-specific genes by qRT-PCR. Microarray analysis of gene expression confirmed the alteration of several differentiation signaling pathways, including the Notch pathway. Using sodium butyrate and post-confluent growth as inducers of differentiation, we demonstrated that MT1G does indeed play a functional role in promoting goblet over enterocyte differentiation in vitro. Labile zinc is also induced upon differentiation of CRC cells, functionally contributing to enterocyte over goblet differentiation, as revealed using zinc-specific chelating agents. Overall, our results uncover a new tumor-suppressor activity of MT1G in promoting the differentiation of at least some CRC tumors, and implicate MTs and zinc signaling as new players in colorectal differentiation. This further contributes to the hypothesis that re-induction of MTs may have therapeutic value by diminishing the aggressiveness of CRC tumors.

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Reduced zinc cytotoxicity following differentiation of neural stem/progenitor cells into neurons and glial cells is associated with upregulation of metallothioneins

Cited by 8 publications

References 24 publications

Enhanced mesenchymal stem cells growth on antibacterial microgrooved electrospun zinc chloride/polycaprolactone conduits for peripheral nerve regeneration

Enhanced mesenchymal stem cells growth on antibacterial microgrooved electrospun zinc chloride/polycaprolactone conduits for peripheral nerve regeneration

Effects of subcytotoxic cadmium on morphology of glial fibrillary acidic protein network in astrocytes derived from murine neural stem/progenitor cells

Metallothionein 1G promotes the differentiation of HT-29 human colorectal cancer cells

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