Rescue of ER oxidoreductase function through polyphenolic phytochemical intervention: implications for subcellular traffic and neurodegenerative disorders

Biochemical and Biophysical Research Communications
Rituraj PalM Narayan

Abstract

Protein disulfide isomerase (PDI), the chief endoplasmic reticulum (ER) resident oxidoreductase chaperone that catalyzes maturation of disulfide-bond-containing proteins is involved in the pathogenesis of both Parkinson's (PD) and Alzheimer's (AD) diseases. S-nitrosylation of PDI cysteines due to nitrosative stress is associated with cytosolic debris accumulation and Lewy-body aggregates in PD and AD brains. We demonstrate that the polyphenolic phytochemicals curcumin and masoprocol can rescue PDI from becoming S-nitrosylated and maintain its catalytic function under conditions mimicking nitrosative stress by forming stable NOx adducts. Furthermore, both polyphenols intervene to prevent the formation of PDI-resistant polymeric misfolded protein forms that accumulate upon exposure to oxidative stress. Our study suggests that curcumin and masoprocol can serve as lead-candidate prophylactics for reactive oxygen species induced chaperone damage, protein misfolding and neurodegenerative disease; importantly, they can play a vital role in sustaining traffic along the ER's secretory pathway by preserving functional integrity of PDI.

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Citations

Aug 23, 2011·The Proceedings of the Nutrition Society·K P ConroyM Warnock
Jun 7, 2011·Drugs & Aging·Melanie-Jayne R Howes, Elaine Perry
May 19, 2012·The FEBS Journal·Mahesh Narayan
Jan 1, 2014·Cell Biology International·Debarshi RoyRituraj Pal
Mar 18, 2016·Cell Biochemistry and Biophysics·Mahmoud F KhalilMahesh Narayan
Dec 7, 2010·Biochemical and Biophysical Research Communications·Rituraj PalMahesh Narayan
Mar 5, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Aiassa VirginiaInés Albesa
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May 5, 2018·Oxidative Medicine and Cellular Longevity·Giuseppina AmodioPaolo Remondelli
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Jan 9, 2019·Frontiers in Oncology·Yonghan HeQingpeng Kong
Jul 15, 2021·Molecular and Cellular Biochemistry·Shreya DasArunima Sengupta

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