Biochemical and Biophysical Research Communications
Oxidative stress promotes mutant huntingtin aggregation and mutant huntingtin-dependent cell death by mimicking proteasomal malfunction
Section snippets
Materials and methods
Materials. Proteasome substrate, MG132, lactacystin, N-acetyl cysteine, rabbit polyclonal ubiquitin antibody, mouse monoclonal β-tubulin, and all cell culture reagents were obtained from Sigma. LipofectAMINE 2000 and ponasterone A were obtained from Invitrogen, mouse monoclonal anti-HA was obtained from Roche, rabbit polyclonal anti-SOD1 and DJ-1 and mouse monoclonal anti-Hsp70 were from Santa Cruz, and AP-conjugated anti-mouse and anti-rabbit IgG were from Vector laboratories. Ubiquitin
Oxidative stimuli enhances mutant huntingtin-induced cell death and mutant huntingtin aggregation
To test the possible effect of oxidative stress on the expanded polyglutamine protein-induced cell death we used stable and inducible cell lines that express tNhtt fused with EGFP containing 16 and 150 polyglutamine residues. The cell lines were named HD 16Q and HD 150Q and their corresponding expressed proteins were named tNhtt-16Q and tNhtt-150Q. The cell lines were induced with 1 μM ponasterone A for 2 days and then exposed to different doses of H2O2 for 5 h. The cell lines were induced for 2
Discussion
Ample evidence indicates that oxidative stress and energy defect may play an important role in the pathogenesis of polyglutamine diseases including HD [9], [10], [11], [12], [13]. Recent studies have also demonstrated the involvement of proteasome impairment in vast majority of neurodegenerative disorders including polyglutamine diseases [7], [8]. But the relationship between oxidative stress and proteasomal malfunction in the polyglutamine diseases is not known. In the present investigation,
Acknowledgments
This work was supported by the Department of Biotechnology, Government of India. P.D. and A.M. were supported by research fellowship from Council of Scientific and Industrial Research, Government of India.
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