A curious case of cysteines in human peroxiredoxin I

Redox Biology

Reena V. Saini¹  Adesh K. Saini²  Priyanka Thakur³  Neeraj K. Saini³  Deepak Sharma³  Rakesh Kumar⁴  Ashu Mohammad⁴  Arpit Gupta⁵  Christine C. Winterbourn⁶ 

[1] Faculty of Applied Science and Biotechnology, Shoolini University, Solan, 173229, India;Centre for Free Radical Research, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand;Council of Scientific and Industrial Research-Institute of Microbial Technology, Chandigarh, India;Department of Biotechnology and Central Research Cell, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, 133207, India;Department of Biotechnology, Jawaharlal Nehru University, Delhi, 110067, India;Faculty of Sciences, Shoolini University, Solan, 173229, India;

关键词: Human peroxiredoxins;    Catalytic residues;    Yeast;    Redox stress;    Chaperone activity;    Saccharomyces cerevisiae;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown