Redox biology of the intestine

Abstract

The intestinal tract, known for its capability for self-renew, represents the first barrier of defense between the organism and its luminal environment. The thiol/disulfide redox systems comprising the glutathione/glutathione disulfide (GSH/GSSG), cysteine/cystine (Cys/CySS) and reduced and oxidized thioredoxin (Trx/TrxSS) redox couples play important roles in preserving tissue redox homeostasis, metabolic functions, and cellular integrity. Control of the thiol-disulfide status at the luminal surface is essential for maintaining mucus fluidity and absorption of nutrients, and protection against chemical-induced oxidant injury. Within intestinal cells, these redox couples preserve an environment that supports physiological processes and orchestrates networks of enzymatic reactions against oxidative stress. In this review, we focus on the intestinal redox and antioxidant systems, their subcellular compartmentation, redox signaling and epithelial turnover, and contribution of luminal microbiota, key aspects that are relevant to understanding redox-dependent processes in gut biology with implications for degenerative digestive disorders, such as inflammation and cancer.

cGMP Signaling Increases Antioxidant Gene Expression by Activating Forkhead Box O3A in the Colon Epithelium

“…7,8 We tested the ability of the cGMP/FoxO pathway to augment the epithelial barrier that had been compromised by treatment with DSS ( Figure 7F). An acute dose of vardenafil (15 hours) was able to reduce the barrier permeability in this model to the level of control animals that had not received any DSS.…”

“…4e6 Inflammatory cytokines and reactive oxygen species (ROS) can further compromise barrier function and set the stage for inflammatory bowel disease and colorectal cancer. 7,8 Oxidative stress arising from ingested chemicals and endogenous microbiota is also barrier disruptive and plays an important role in carcinogenesis in the colon. 9e12 In this stressful microenvironment, the antioxidant machinery of the intestinal epithelium has an important role in preserving reduction-oxidation (redox) balance and cellular integrity.…”

“…9e12 In this stressful microenvironment, the antioxidant machinery of the intestinal epithelium has an important role in preserving reduction-oxidation (redox) balance and cellular integrity. 8 Uroguanylin and guanylin are endogenous peptide hormones that trigger intracellular cGMP production by activating guanylyl cyclase C receptors (GC-C) in the intestinal epithelium. 13,14 This system is well established in the regulation of fluid and electrolyte balance, 15 but has emerged more recently as fundamentally important for the maintenance of epithelial homeostasis and barrier integrity.…”

Crucial Role of FLVCR1a in the Maintenance of Intestinal Heme Homeostasis

“…The maintenance of the intestinal epithelial redox environment is essential for the activities of key physiological processes that include digestion and absorption, cell proliferation and apoptosis, and immune response. The fine tuning of the extracellular redox environment is also crucial in the intestinal stem cell niche that signals intestinal cell genesis (5). Accordingly, the disruption of intestinal redox homeostasis has been associated to the development of gut disorders (1,36), among which intestinal ulcers and cancer.…”

Proteomic proof that a probiotic elevates glutathione level in human serum

“…Several approaches have been tried to improve the human body´s glutathione status starting with oral supplementation. Although it proved to be ineffective years ago [22], researchers continue to test the version [44], probably encouraged by the ability of apical membrane cells to uptake GSH [45]. Lipoceutical and transdermal vehicles as well as nanoparticles are also in testing phase [46,47].…”