Molecular mechanisms of Mn induced neurotoxicity: RONS generation, genotoxicity, and DNA‐damage response. Issue 7 (14th March 2013)

• Record Type: Journal Article
• Authors: Bornhorst, Julia; Meyer, Sören; Weber, Till; Böker, Carolina; Marschall, Talke; Mangerich, Aswin; Beneke, Sascha; Bürkle, Alexander; Schwerdtle, Tanja
• Is Part Of: Molecular nutrition & food research. Volume 57:Issue 7(2013:Jul.)
• Page Start: 1255
• Page End: 1269
• Publication Date: 2013-03-14
• Subjects: Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201200758
• Languages: English
• ISSNs: 1613-4125

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mnfr1957-sec-0010" sec-type="section"> <title>Scope</title> <p>In industrial countries dietary manganese (Mn) intake is well above the estimated average requirement. Moreover, exposure to high Mn levels is known to cause adverse neurological effects in humans, which are yet mechanistically not well understood.</p> </sec> <sec id="mnfr1957-sec-0020" sec-type="section"> <title>Methods and results</title> <p>This study aimed to identify early modes of action of Mn induced toxicity in mammalian brain cells. In primary porcine brain capillary endothelial cells induction of reactive oxygen and nitrogen species was identified as the most sensitive endpoint (≥0.5 μM MnCl<sub>2</sub>). In cultured human astrocytes MnCl<sub>2</sub> was rapidly bioavailable, induced a slight increase of cellular reactive oxygen and nitrogen species levels and a slight decrease of ATP levels (1–100 μM MnCl<sub>2</sub>), while no genotoxic effects were observed. However, MnCl<sub>2</sub> (≥1 μM) efficiently disturbed DNA‐damage‐induced poly(ADP‐ribosyl)ation in human astrocytes, which indicates sensitization of cells to genotoxic treatment. Additionally, we determined Mn levels in infant formula, which are generally massively supplemented with Mn and thus might pose an important source for Mn overexposure.</p> </sec> <sec id="mnfr1957-sec-0030" sec-type="section"> <title>Conclusion</title> <p>The observed inhibition of DNA‐damage‐induced poly(ADP‐ribosyl)ation in human astrocytes by exposure‐relevant Mn concentrations indicate that in terms of Mn the existing guidelines for infant formula but also drinking water should be critically reconsidered.</p> </sec> </abstract>