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Inhibition of MAPK Hog1 Results in Increased Hsp104 Aggregate Formation Probably through Elevated Arsenite Influx into the Cells, an Approach with Numerous Potential Applications

Journal article
Authors Doryaneh Ahmadpour
Amin Abbaszadehbanaeiyan
Morten Grøtli
Martin Adiels
Mattias Goksör
Caroline B. Adiels
Published in American Journal of Molecular Biology
Volume 4
Issue 2
Pages 59-71
ISSN 2161-6620
Publication year 2014
Published at Department of Mathematical Sciences
Department of Chemistry and Molecular Biology
Department of Physics (GU)
Pages 59-71
Language en
Links dx.doi.org/10.4236/ajmb.2014.42008
https://gup.ub.gu.se/file/149242
Keywords Mitogen Activated Protein Kinase (MAPK), Hog1, MAPK inhibitor, Arsenic, Microfluidics
Subject categories Biological Sciences, Biophysics, Molecular biophysics, Cell Biology

Abstract

Arsenic is a highly toxic and carcinogenic metalloid widely dispersed in the environment, contaminating water and soil and accumulating in crops. Paradoxically, arsenic is also part of modern therapy and employed in treating numerous ailments and diseases. Hence, inventing strategies to tune cellular arsenic uptake based on purpose is striking. Here, we describe an approach in which the arsenite uptake can be increased using a MAPK inhibitor. Employing microfluidic flow chambers in combination with optical tweezers and fluorescent microscopy, we elevated the influx of arsenite into the yeast Saccharomyces cerevisiae cells following short-term treatment with a Hog1 kinase inhibitor. The increase in arsenite uptake was followed on arsenite triggered redistribution of a reporter protein, Hsp104-GFP, which was imaged over time. The effect was even more pronounced when the yeast mother and daughter cells were analyzed disjointedly, an opportunity provided owing to single-cell analysis. Our data firstly provide a strategy to increase arsenite uptake and secondly show that arsenite triggered aggregates, previously shown to be sites of damaged proteins, are distributed asymmetrically and less accumulated in daughter cells. Inventing approaches to tune arsenite uptake has a great value for its use in environmental as well as medical applications.

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