Cell Stress and Chaperones

, Volume 19, Issue 5, pp 667–673 | Cite as

Activation of salt shock response leads to solubilisation of mutant huntingtin in Saccharomyces cerevisiae

  • Aliabbas A. Saleh
  • Ankan Kumar Bhadra
  • Ipsita Roy
Original Paper
First Online:
Received:
Revised:
Accepted:

Abstract

Formation of cytoplasmic and nuclear aggregates is a hallmark of Huntington’s disease (HD). Inhibition of aggregation of mutant huntingtin has been suggested to be a feasible approach to slow down the progress of this neurodegenerative disorder. Exposure to environmental stimuli leads to the activation of the stress response machinery of the cell. In this work, we have investigated the effect of salt shock on the aggregation of mutant huntingtin (103Q-htt) in a yeast model of HD. We found that at an optimum concentration of NaCl, the protein no longer formed aggregates and existed in the soluble form. This led to lower oxidative stress in the cell. Salt shock resulted in the synthesis of the osmolyte glycerol, which was partially responsible for the beneficial effect of stress. Surprisingly, we also found increase in the synthesis of another osmolyte, trehalose. Using deletion strains, we were able to show that the effect on solubilisation of mutant huntingtin is due to the synthesis of optimum amounts of both osmolytes. Stress-induced effect was monitored on gene expression. Genes related to proteins of the osmosensory pathway were upregulated on exposure to salt while those coding for stress response proteins were downregulated when solubilisation of mutant huntingtin occurred. Our study shows that activation of stress response elements can have beneficial effect in the solubilisation of huntingtin in a yeast model of HD.

Keywords

Glycerol Huntingtin Huntington’s disease Salt shock Trehalose 
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Notes

Acknowledgments

The authors are thankful to Prof. Michael Y. Sherman, Boston University School of Medicine, Boston, Massachusetts, USA, for the gift of pYES2-103Q-htt. The work was partially supported by a research grant [SR/SO/HS/0101/2010] from Department of Science and Technology. Technical help provided by Uma S. Gune is gratefully acknowledged. AAS is grateful to Council for Scientific and Industrial Research (CSIR) for the award of senior research fellowship. AKB acknowledges the award of senior research fellowship by DST-INSPIRE programme.

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Copyright information

© Cell Stress Society International 2014

Authors and Affiliations

  • Aliabbas A. Saleh
    • 1
  • Ankan Kumar Bhadra
    • 1
  • Ipsita Roy
    • 1
  1. 1.Department of BiotechnologyNational Institute of Pharmaceutical Education and Research (NIPER)NagarIndia

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