Role of Heme Oxygenase in Gastrointestinal Epithelial Cells

Abstract

The gastrointestinal tract is a unique organ containing both vascular and luminal routes lined by epithelial cells forming the mucosa, which play an important role in the entry of nutrients and act as a selective barrier, excluding potentially harmful agents. Mucosal surfaces establish a selective barrier between hostile external environments and the internal milieu. Heme is a major nutritional source of iron and is a pro-oxidant that causes oxidative stress. Heme oxygenases (HOs) catalyze the rate-limiting step in heme degradation, resulting in the formation of iron, carbon monoxide, and biliverdin, which are subsequently converted to bilirubin by biliverdin reductase. In gastrointestinal pathogenesis, HO-1, an inducible isoform of HO, is markedly induced in epithelial cells and plays an important role in protecting mucosal cells. Recent studies have focused on the biological effects of the products of this enzymatic reaction, which have antioxidant, anti-inflammatory, and cytoprotective functions. In this review, the essential roles of HO in the gastrointestinal tract are summarized, focusing on nutrient absorption, protection against cellular stresses, and the maintenance and regulation of tight junction proteins, emphasizing the potential therapeutic implications. The biochemical basis of the potential therapeutic implications of glutamine for HO-1 induction in gastrointestinal injury is also discussed.

Use of Microalgae-Derived Astaxanthin to Improve Cytoprotective Capacity in the Ileum of Heat-Induced Oxidative Stressed Broilers

“…MUC2 is located both intracellular and extracellular of the membrane as a supramolecular fiber for protein, virion and antigen binding for maintenance of the gastrointestinal epithelium through intestinal cholesterol homeostasis and macrophage activation involving the immune response (Table 5) [28,29,36]. The results support that AST may help maintain the integrity of the mucus barrier in the gastrointestinal tract for protection of the epithelial surfaces as indicated by the upregulation of the HSAX over the HS group.…”

“…It interacts with gut microbiota to balance beneficial and harmful microbes, supporting a healthy mucosa. Mucosal immune responses defend against pathogens and support beneficial bacteria, contributing to a healthy and functional barrier in the small intestine [28,29].…”

Pathological significance of heme oxygenase-1 as a potential tumor promoter in heme-induced colorectal carcinogenesis

“…Increasing intracellular heme and excess luminal heme at the apical membrane stimulates the activation of antioxidant signaling pathways, such as HMOX1 upregulation. 37 However, the resulting upregulation of HMOX1 may be inadequate owing to the overwhelming luminal cytotoxicity and resulting oxidative injury to the colon epithelia. Thus, the HMOX1 cytoprotective effect may be conditional and depend on the extent of the oxidative agent burden that the cellular environment can tolerate.…”

Redox and Metabolic Regulation of Intestinal Barrier Function and Associated Disorders

“…While a minimum amount of H 2 S has anti-inflammatory effects [22], higher levels of luminal H 2 S are detrimental to mucus layer integrity and are involved in colorectal carcinogenesis [23]. Carbon monoxide (CO), a product of heme oxygenase, is associated with anti-inflammatory, anti-apoptotic and cytoprotective effects [24]. CO protects intestinal epithelial integrity by up-regulating TJ protein expression and reducing pro-inflammatory cytokines.…”