Journal article

Inhibition of APE1/Ref-1 Redox Signaling Alleviates Intestinal Dysfunction and Damage to Myenteric Neurons in a Mouse Model of Spontaneous Chronic Colitis

Lauren Sahakian, Rhiannon T Filippone, Rhian Stavely, Ainsley M Robinson, Xu Sean Yan, Raquel Abalo, Rajaraman Eri, Joel C Bornstein, Mark R Kelley, Kulmira Nurgali

INFLAMMATORY BOWEL DISEASES | OXFORD UNIV PRESS INC | Published : 2021

Abstract

BACKGROUND: Inflammatory bowel disease (IBD) associates with damage to the enteric nervous system (ENS), leading to gastrointestinal (GI) dysfunction. Oxidative stress is important for the pathophysiology of inflammation-induced enteric neuropathy and GI dysfunction. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a dual functioning protein that is an essential regulator of the cellular response to oxidative stress. In this study, we aimed to determine whether an APE1/Ref-1 redox domain inhibitor, APX3330, alleviates inflammation-induced oxidative stress that leads to enteric neuropathy in the Winnie murine model of spontaneous chronic colitis. METHODS: Winnie mice receiv..

View full abstract

Grants

Awarded by National Institute of Health


Awarded by DOD


Funding Acknowledgements

This work was supported by the Institute for Health and Sport, Victoria University. MRK was supported by grants from the National Institute of Health CA167291, CA205166, CA231267, HL140961, and DOD grant W81XWH1910217; he is also supported by the Riley Children's Foundation and the Tom Wood Lexus Foundation.