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  1. Article ; Online: New insights into manganese toxicity and speciation.

    Michalke, Bernhard / Fernsebner, Katharina

    Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)

    2013  Volume 28, Issue 2, Page(s) 106–116

    Abstract: Manganese (Mn) is known to be a neurotoxic agent for nearly 175 years now. A lot of research has therefore been carried out over the last century. From preliminary describing only symptoms of Mn-(over)exposed workers, research was preceded to more detail ...

    Abstract Manganese (Mn) is known to be a neurotoxic agent for nearly 175 years now. A lot of research has therefore been carried out over the last century. From preliminary describing only symptoms of Mn-(over)exposed workers, research was preceded to more detail on toxic mechanisms of Mn. Unraveling those neurotoxic mechanisms implicated a number of studies, which were summarized partly in several reviews (e.g. Yokel RA. Neuromol Med 2009;11(4):297-310; Aschner M, et al. Toxicology Appl Pharmacol 2007;221(2):131-47; Michalke B, et al. J Environ Monit 2007;9(7):650). Since our recent review on Mn-speciation in 2007 (Michalke B, et al. J Environ Monit 2007;9(7):650), Mn-research was considerably pushed forward and several new research articles were published. The very recent years though, Mn toxicity investigating science is spreading into different fields with very detailed and complex study designs. Especially the mechanisms of Mn-induced neuronal injury on cellular and molecular level was investigated in more detail, discussing neurotransmitter and enzyme interactions, mechanisms of action on DNA level and even inclusion of genetic influences. Depicting the particular Mn-species was also a big issue to determine which molecule is transporting Mn at the cell membranes and which one is responsible for the injury of neuronal tissue. Other special foci on epidemiologic studies were becoming more and more important: These foci were directed toward environmental influences of Mn on especially Parkinson disease prevalence and the ability to carry out follow-up studies about Mn-life-span exposure. All these very far-reaching research applications may finally lead to a suitable future human Mn-biomonitoring for being able to prevent or at least detect the early onset of manganism at the right time.
    MeSH term(s) Cells/drug effects ; Cells/metabolism ; Environmental Monitoring ; Epidemiologic Studies ; Humans ; Manganese/toxicity
    Chemical Substances Manganese (42Z2K6ZL8P)
    Language English
    Publishing date 2013-09-14
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1236267-0
    ISSN 1878-3252 ; 1611-602X ; 0946-672X
    ISSN (online) 1878-3252 ; 1611-602X
    ISSN 0946-672X
    DOI 10.1016/j.jtemb.2013.08.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Manganese leads to an increase in markers of oxidative stress as well as to a shift in the ratio of Fe(II)/(III) in rat brain tissue.

    Fernsebner, Katharina / Zorn, Julia / Kanawati, Basem / Walker, Alesia / Michalke, Bernhard

    Metallomics : integrated biometal science

    2014  Volume 6, Issue 4, Page(s) 921–931

    Abstract: Occupationally or environmentally caused chronic exposure to Manganese (Mn) can lead to a degeneration of dopaminergic neurons inducing a Parkinson-like complaint called manganism. Deciphering the ongoing neurodegenerative mechanisms in the affected ... ...

    Abstract Occupationally or environmentally caused chronic exposure to Manganese (Mn) can lead to a degeneration of dopaminergic neurons inducing a Parkinson-like complaint called manganism. Deciphering the ongoing neurodegenerative mechanisms in the affected brain is still a major task for understanding the complex modes of action. Therefore, we applied a non-toxic, oral feeding in rats simulating a chronic exposure to Mn. Analysis of brain extracts by electrospray ionization Fourier transform resonance mass spectrometry (ESI-FT-ICR-MS) revealed an increase in markers of oxidative stress like glutathione disulfide (GSSG), prostaglandins, and 15(S)-HETE, a marker of lipid peroxidation. Furthermore, acetylcholinesterase (AchE) activity and glutamate concentrations were elevated in brain samples of Mn-supplemented rats, suggesting oxidative stress in the brain tissue. Application of ion chromatography coupled to inductively coupled plasma-optical emission spectrometry (IC-ICP-OES) further showed a shift of Fe(III) towards Fe(II) in the brain samples enabling for example the action of the Fenton reaction. This is the first time that changes in the Fe-species distribution could be related to Mn-induced neuroinflammation and is therefore enlarging the knowledge of this complex neurodegenerative condition. The combination of our findings provides substantial evidence that Mn-induced neuroinflammation leads to oxidative stress triggered by multifactorial pathophysiological processes.
    MeSH term(s) Animals ; Brain/metabolism ; Brain Chemistry ; Eating ; Ferric Compounds/analysis ; Ferric Compounds/metabolism ; Ferrous Compounds/analysis ; Ferrous Compounds/metabolism ; Glutamic Acid/analysis ; Glutamic Acid/metabolism ; Male ; Manganese/metabolism ; Manganese/toxicity ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Ferric Compounds ; Ferrous Compounds ; Glutamic Acid (3KX376GY7L) ; Manganese (42Z2K6ZL8P)
    Language English
    Publishing date 2014-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2474317-3
    ISSN 1756-591X ; 1756-5901
    ISSN (online) 1756-591X
    ISSN 1756-5901
    DOI 10.1039/c4mt00022f
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Dissecting the impact of Frizzled receptors in Wnt/β-catenin signaling of human mesenchymal stem cells.

    Kolben, Thomas / Peröbner, Iris / Fernsebner, Katharina / Lechner, Felix / Geissler, Claudia / Ruiz-Heinrich, Lourdes / Capovilla, Simon / Jochum, Marianne / Neth, Peter

    Biological chemistry

    2012  Volume 393, Issue 12, Page(s) 1433–1447

    Abstract: Wnt/β-catenin signaling is of fundamental importance in the regulation of self-renewal, migration/invasion, and differentiation of human mesenchymal stem cells (hMSCs). Because little information is available about the function of Frizzled receptors ( ... ...

    Abstract Wnt/β-catenin signaling is of fundamental importance in the regulation of self-renewal, migration/invasion, and differentiation of human mesenchymal stem cells (hMSCs). Because little information is available about the function of Frizzled receptors (Fzds) as the main receptors of Wnt proteins in hMSCs, we first performed comparative Fzd mRNA expression profiling. Fzd9 and Fzd10 were not expressed in hMSCs. While Fzd3 was expressed at low levels in hMSCs, the other Fzds exhibited high expression rates. Activation and repression of Wnt signaling in hMSCs revealed that the expression levels of Fzd1, Fzd6, and Fzd7 are positively correlated with the Wnt/β-catenin activation status, whereas Fzd8 exhibited an inverse relation. For studying the functional relevance of Fzds in Wnt/β-catenin signaling, RNA interference, ectopic expression studies, and rescue approaches were performed in hMSCs carrying a highly sensitive TCF/LEF reporter gene system (Gaussia luciferase). We found that, Fzd1, Fzd5, Fzd7, and Fzd8 are largely involved in Wnt/β-catenin signaling of hMSCs. Moreover, the knockdown of Fzd5 can be compensated by the ectopic expression of Fzd7. Conversely, the ectopic expression of Fzd5 in Fzd7-knockdown hMSCs resulted in a rescue of Wnt/β-catenin signaling, pointing to a functional redundancy of Fzd5 and Fzd7.
    MeSH term(s) Adult ; Cells, Cultured ; Frizzled Receptors/genetics ; Frizzled Receptors/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Genes, Reporter ; Humans ; Male ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/metabolism ; RNA Interference ; RNA, Messenger/genetics ; Signal Transduction ; TCF Transcription Factors/genetics ; TCF Transcription Factors/metabolism ; Wnt Proteins/metabolism ; beta Catenin/metabolism
    Chemical Substances Frizzled Receptors ; RNA, Messenger ; TCF Transcription Factors ; Wnt Proteins ; beta Catenin
    Language English
    Publishing date 2012-12
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1334659-3
    ISSN 1437-4315 ; 1431-6730 ; 1432-0355
    ISSN (online) 1437-4315
    ISSN 1431-6730 ; 1432-0355
    DOI 10.1515/hsz-2012-0186
    Database MEDical Literature Analysis and Retrieval System OnLINE

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