title: Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Nexus Implicated in Bowel Disease Pathophysiology.
abstract: The endoplasmic reticulum (ER) is a complex protein folding and trafficking organelle. Alteration and discrepancy in the endoplasmic reticulum environment can affect the protein folding process and hence, can result in the production of misfolded proteins. The accumulation of misfolded proteins causes cellular damage and elicits endoplasmic reticulum stress. Under such stress conditions, cells exhibit reduced functional synthesis, and will undergo apoptosis if the stress is prolonged. To resolve the ER stress, cells trigger an intrinsic mechanism called an unfolded protein response (UPR). UPR is an adaptive signaling process that triggers multiple pathways through the endoplasmic reticulum transmembrane transducers, to reduce and remove misfolded proteins and improve the protein folding mechanism, in order to improve and maintain endoplasmic reticulum homeostasis. An increasing number of studies support the view that oxidative stress has a strong connection with ER stress. During the protein folding process, reactive oxygen species are produced as by-products, leading to impaired reduction-oxidation (redox) balance conferring oxidative stress. As the protein folding process is dependent on redox homeostasis, the oxidative stress can disrupt the protein folding mechanism and enhance the production of misfolded proteins, causing further ER stress. It is proposed that endoplasmic reticulum stress and oxidative stress together play significant roles in the pathophysiology of bowel diseases.
authors.affiliation: School of Health Science, University of Tasmania, Newnham TAS 7248, Australia. chongwc1993@gmail.com.
authors.forename: Wai Chin
authors.initials: WC
authors.lastname: Chong
authors.affiliation: School of Health Science, University of Tasmania, Newnham TAS 7248, Australia. Madhur.Shastri@utas.edu.au.
authors.forename: Madhur D
authors.initials: MD
authors.lastname: Shastri
authors.affiliation: School of Health Science, University of Tasmania, Newnham TAS 7248, Australia. rderi@utas.edu.au.
authors.forename: Rajaraman
authors.initials: R
authors.lastname: Eri
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D006706:Homeostasis; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D018384:Oxidative Stress; D017510:Protein Folding; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D017382:Reactive Oxygen Species
keywords: antioxidant mechanisms; endoplasmic reticulum stress; inflammatory bowel disease; misfolded protein; oxidative stress; unfolded protein response