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A curious case of cysteines in human peroxiredoxin I

Authors :
Ashu Mohammad
Reena V. Saini
Rakesh Kumar
Deepak Sharma
Neeraj K. Saini
Arpit Gupta
Priyanka Thakur
Christine C. Winterbourn
Adesh K. Saini
Source :
Redox Biology, Vol 37, Iss , Pp 101738- (2020)
Publication Year :
2020
Publisher :
Elsevier, 2020.

Abstract

Peroxiredoxins (Prxs) are antioxidant proteins that are involved in cellular defence against reactive oxygen species and reactive nitrogen species. Humans have six peroxiredoxins, hPrxI-VI, out of which hPrxI and hPrxII belongs to the typical 2-Cys class sharing 90% conservation in their amino acid sequence including catalytic residues required to carry out their peroxidase and chaperone activities. Despite the high conservation between hPrxI and hPrxII, hPrxI behaves differently from hPrxII in its peroxidase and chaperone activity. We recently showed in yeast that in the absence of Tsa1 and Tsa2 (orthologs of hPrx) hPrxI protects the cells against different stressors whereas hPrxII does not. To understand this difference, we expressed catalytic mutants of hPrxI in yeast cells lacking the orthologs of hPrxI/II. We found that the catalytic mutants lacking peroxidase function including hPrxIC52S, hPrxIC173S, hPrxIT49A, hPrxIP45A and hPrxIR128A were not able to grow on media with nitrosative stressor (sodium nitroprusside) and unable to withstand heat stress, but surprisingly they were able to grow on an oxidative stressor (H2O2). Interestingly, we found that hPrxI increases the expression of antioxidant genes, GPX1 and SOD1, and this is also seen in the case of a catalytic mutant, indicating hPrxI can indirectly reduce oxidative stress independently of its own peroxidase function and thus suggesting a novel role of hPrxI in altering the expression of other antioxidant genes. Furthermore, hPrxIC83T was resistant to hyperoxidation and formation of stable high molecular weight oligomers, which is suggestive of impaired chaperone activity. Our results suggest that the catalytic residues of hPrxI are essential to counter the nitrosative stress whereas Cys83 in hPrxI plays a critical role in hyperoxidation of hPrxI.

Details

Language :
English
ISSN :
22132317
Volume :
37
Issue :
101738-
Database :
Directory of Open Access Journals
Journal :
Redox Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.4c44429944947ad9c244bf6773082c7
Document Type :
article
Full Text :
https://doi.org/10.1016/j.redox.2020.101738