Peroxiredoxin 1 plays a primary role in protecting pancreatic β-cells from hydrogen peroxide and peroxynitrite. Am J Physiol Regul Integr Comp Physiol 2020 May 01;318(5):R1004-R1013
Date
04/16/2020Pubmed ID
32292063Pubmed Central ID
PMC7272767DOI
10.1152/ajpregu.00011.2020Scopus ID
2-s2.0-85084379321 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
Both reactive nitrogen and oxygen species (RNS and ROS), such as nitric oxide, peroxynitrite, and hydrogen peroxide, have been implicated as mediators of pancreatic β-cell damage during the pathogenesis of autoimmune diabetes. While β-cells are thought to be vulnerable to oxidative damage due to reportedly low levels of antioxidant enzymes, such as catalase and glutathione peroxidase, we have shown that they use thioredoxin reductase to detoxify hydrogen peroxide. Thioredoxin reductase is an enzyme that participates in the peroxiredoxin antioxidant cycle. Peroxiredoxins are expressed in β-cells and, when overexpressed, protect against oxidative stress, but the endogenous roles of peroxiredoxins in the protection of β-cells from oxidative damage are unclear. Here, using either glucose oxidase or menadione to continuously deliver hydrogen peroxide, or the combination of dipropylenetriamine NONOate and menadione to continuously deliver peroxynitrite, we tested the hypothesis that β-cells use peroxiredoxins to detoxify both of these reactive species. Either pharmacological peroxiredoxin inhibition with conoidin A or specific depletion of cytoplasmic peroxiredoxin 1 (Prdx1) using siRNAs sensitizes INS 832/13 cells and rat islets to DNA damage and death induced by hydrogen peroxide or peroxynitrite. Interestingly, depletion of peroxiredoxin 2 (Prdx2) had no effect. Together, these results suggest that β-cells use cytoplasmic Prdx1 as a primary defense mechanism against both ROS and RNS.
Author List
Stancill JS, Happ JT, Broniowska KA, Hogg N, Corbett JAAuthors
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinNeil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCell Death
Cell Line, Tumor
Cytoplasm
Cytoprotection
DNA Damage
Enzyme Inhibitors
Hydrogen Peroxide
Insulin-Secreting Cells
Male
Oxidative Stress
Peroxiredoxins
Peroxynitrous Acid
Quinoxalines
RNA Interference
RNA, Small Interfering
Rats, Sprague-Dawley
Signal Transduction
Thioredoxin Reductase 1
