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- Title
ER Protein Processing Under Oxidative Stress: Implications and Prevention.
- Authors
Khalil, Mahmoud; Valenzuela, Carlos; Sisniega, Daniella; Skouta, Rachid; Narayan, Mahesh
- Abstract
Elevated levels of mitochondrial nitrosative stress have been associated with the pathogenesis of both Parkinson's and Alzheimer's diseases. The mechanism involves catalytic poisoning of the endoplasmic reticulum (ER)-resident oxidoreductase chaperone, protein disulfide isomerase (PDI), and the subsequent accumulation of ER-processed substrate proteins. Using a model system to mimic mitochondrial oxidative and nitrosative stress, we demonstrate a PDI-independent mechanism whereby reactive oxygen species (ROS) compromise regeneration rates of disulfide bond-containing ER-processed proteins. Under ROS-duress, the secretion-destined traffic adopts disulfide-exposed structures making the protein flux retrotranslocation biased. We also demonstrate that ROS-compromised protein maturation rates can be rescued by the polyphenol ellagic acid (EA). Our results are significant in that they reveal an additional mechanism which could promote neurodegenerative disorders. Furthermore, our data reveal that EA possesses therapeutic potential as a lead prophylactic agent against oxidative/nitrosative stress-related neurodegenerative diseases.
- Subjects
OXIDATIVE stress; ENDOPLASMIC reticulum; OXIDOREDUCTASES; PROTEIN disulfide isomerase; ISOMERASES
- Publication
Cell Biochemistry & Biophysics, 2016, Vol 74, Issue 2, p213
- ISSN
1085-9195
- Publication type
Article
- DOI
10.1007/s12013-016-0726-9