Upregulation of DMT1 expression in choroidal epithelia of the blood–CSF barrier following manganese exposure in vitro

Wang, Xueqian; Li, Guojun Jane; Zheng, Wei

doi:10.1016/j.brainres.2006.04.046

Cited by 54 publications

(63 citation statements)

References 48 publications

(64 reference statements)

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“…This elevation in DMT1 expression is not region-specific; nonetheless, the data directly relate the effect of an enhanced Mn diet with augmentation in DMT1 expression (Garcia et al, 2006). In addition, this correlation is supported by in vitro data where exposure to Mn for 24 and 48 hours has been shown to increase DMT1 expression in the immortalized choroidal epithelial Z310 cell line by 45% and 78% respectively (Wang et al, 2006). …”

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confidence: 61%

Manganese transport in eukaryotes: The role of DMT1

2008

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Manganese (Mn) is a transition metal that is essential for normal cell growth and development, but is toxic at high concentrations. While Mn deficiency is uncommon in humans, Mn toxicity is known to be readily prevalent due to occupational overexposure in miners, smelters and possibly welders. Excessive exposure to Mn can cause Parkinson's disease-like syndrome; patients typically exhibit extrapyramidal symptoms that include tremor, rigidity and hypokinesia (Calne et al., 1994;Dobson et al., 2004).Mn-induced motor neuron diseases have been the subjects of numerous studies; however, this review is not intended to discuss its neurotoxic potential or its role in the etiology of motor neuron disorders. Rather, it will focus on Mn uptake and transport via the orthologues of the divalent metal transporter (DMT1) and its possible implications to Mn toxicity in various categories of eukaryotic systems, such as in vitro cell lines, in vivo rodents, the fruitfly, Drosophila melanogaster, the honeybee, Apis mellifera L., the nematode, Caenorhabditis elegans, and the baker's yeast, Saccharomyces cerevisiae. Keywords DMT1; Manganese; NRAMP-2; Transport ManganeseMn is one of the most abundant naturally occurring elements in the earth's crust; it does not occur naturally in a pure state. Oxides, carbonates and silicates are the most important Mncontaining minerals (Post, 1999). Depending on its oxidation state, Mn is utilized in countless industrial processes, such as the production of dry cell batteries, steel (Post, 1999; Saric, 1986), fuel oil additives and antiknock agents (Pfeifer et al., 2004;Ressler et al., 1999;Rollin et al., 2005). *Corresponding Author: Michael Aschner, PhD, 2215-B Garland Avenue, 11425 MRB IV, Vanderbilt University Medical Center, Nashville, michael.aschner@vanderbilt.edu. Publisher's Disclaimer: 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 citable 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. NIH Public Access Author ManuscriptNeurotoxicology. Author manuscript; available in PMC 2009 July 1. Published in final edited form as:Neurotoxicology. 2008 July ; 29(4): 569-576. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe major source of Mn in humans is through dietary ingestion. Approximately 3-5% of ingested Mn is absorbed across the intestinal wall, and the remainder is excreted in feces, representing tight homeostatic control over Mn absorption. Mn toxicity from dietary intake is rare; its uptake is tightly regulated, and any excess of ingested Mn is readily excreted via the bile. In contrast, both pulmonary uptake and particulate transport via the olfactory bulb (Saric, 1986;Aschner et al., 1991...

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confidence: 61%

Manganese transport in eukaryotes: The role of DMT1

2008

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“…Data showed that mRNA levels of DMT1, Mdr1b, Oat3, and OB-Ra in choroid plexus tissue were significantly higher than those in Z310 cells when cultured regularly on 6-well plate. Our previous studies have also demonstrated that Z310 cells possess both DMT-1 and TTR proteins (Zheng & Zhao, 2002;Wang, et al 2006).…”

Section: Mrna Expression Of Representative Transporters In Z310 Cellsmentioning

confidence: 79%

Use of Z310 cells as an in vitro blood–cerebrospinal fluid barrier model: Tight junction proteins and transport properties

Shi

Wang

et al. 2008

Toxicology in Vitro

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Immortalized rat choroidal epithelial Z310 cells have the potential to become an in vitro model for studying transport of materials at blood-cerebrospinal fluid barrier (BCB) (Shi and Zheng, Brain Research 1057:37-48, 2005). This study was designed to demonstrate the presence of tight junction properties in Z310 cells and the functionality of Z310 monolayer in transport of selected model compounds. Western blot analyses revealed the presence of claudin-1, ZO-1, and occludin in Z310 cells. Transmission electron microscopy showed a "tight junction" type of structure in the sub-apical lateral membranes between adjacent Z310 cells. Real-time RT-PCR revealed that Z310 cells expressed representative transporters such as DMT1, MTP1, TfR, p-glycoprotein, ATP7A, ZnT1, ABCC1, Oat3, OCT1 and OB-Ra. Moreover, Z310 cells cultured in a two-chamber Transwell device possessed the ability to transport zidovudine (anionic drug), thyroxine (hormone), thymidine (nucleoside), and leptin (large polypeptide) with kinetic properties similar to those obtained from the in vitro model based on primary culture of choroidal epithelial cells. Taken together, these data indicate that the Z310 BCB model expresses major tight junction proteins and forms a tight barrier in vitro. The model also exhibits the ability to transport substances of various categories across the barrier.

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“…44, many transporters are expressed in the CP and are therefore discussed to contribute to Mn transport. Because DMT1 has been shown to be present in the blood-CSF barrier in several studies and Mn exposure resulted in an increased DMT1 expression in rats (52), the present study intended to assess the role of DMT1 in Mn transfer processes. However, applying the DMT1 inhibitor NSC306711, our data show that in the applied in vitro system DMT1 is not the major transporter for Mn uptake into the brain via the blood-CSF barrier.…”

Section: Discussionmentioning

confidence: 99%

Impact of Manganese on and Transfer across Blood-Brain and Blood-Cerebrospinal Fluid Barrier in Vitro

Bornhorst

Wehe

Hüwel

et al. 2012

Journal of Biological Chemistry

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Background: Modes of neurotoxic action after Mn overexposure are not fully understood. Results:The blood-CSF barrier showed higher Mn sensitivity and active Mn transport properties. Conclusion:The blood-CSF barrier might be the major route for Mn into the brain. Significance: Deeper insight in the impact of Mn on and its transfer across brain barrier systems might help to prevent irreversible neurological damage.

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Upregulation of DMT1 expression in choroidal epithelia of the blood–CSF barrier following manganese exposure in vitro

Cited by 54 publications

References 48 publications

Manganese transport in eukaryotes: The role of DMT1

Manganese transport in eukaryotes: The role of DMT1

Use of Z310 cells as an in vitro blood–cerebrospinal fluid barrier model: Tight junction proteins and transport properties

Impact of Manganese on and Transfer across Blood-Brain and Blood-Cerebrospinal Fluid Barrier in Vitro

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