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Heme Oxygenase-1 in Kidney Health and Disease
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Pu Duann, Elias A. Lianos, Pei-Hui Lin
Heme oxygenase (HO) is the rate limiting enzyme catalyzing oxidative cleavage, with electrons delivered from NADPH via cytochrome P450 reductase (CPR), of the porphyrin ring of heme into equimolar by-products of ferrous iron (Fe2+), carbon monoxide (CO) and biliverdin (2) (Figure 1). Biliverdin is quickly converted by biliverdin reductase (BVR) into bilirubin which is ultimately expelled from body (11). Three different isoforms of heme oxygenase (HO) have been reported in mammalian, including the inducible HO-1 (encoded by HMOX1 gene) (12), the homeostatic low level and constitutively active HO-2 isoform (encoded by HMOX2 gene) (13), and the non-enzymatic HO-3 originally identified in rat brain (14). Based on phylogenic alignment, HO-3 evolved as a splicing variant from the HO-2 gene which binds heme but is deprived of catalytic activity (15). Both HO-1 and HO-2 are ubiquitously expressed and catalytically active. HO-2 is present in relatively high concentration in the brain, testis, and vascular endothelial cells (16,17), while HO-1 is more widely distributed. HO-1 is abundant in tissues rich with its substrate heme expression, such as muscle, erythroid-phagocytic system (liver and bone marrow) and spleen where abundant heme was released from senescent RBC processing and hemoglobin recycling for new heme synthesis (18,19).
Micronutrients in the Prevention and Improvement of the Standard Therapy for Alzheimer’s Disease
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
A review showed that markers of oxidative stress, such as protein nitrotyrosine, carbonyls in proteins, lipid oxidation products, and oxidized DNA bases were elevated in the autopsied brain tissue of patients with AD.5 A number of observations substantiate the presence of high levels of oxidative stress in patients with AD. For example, (a) higher expression of heme oxygenase-1 is found in the brains of AD patients161; (b) increased consumption of oxygen is found in AD patients162; (c) increased activity of glucose-6-phosphate dehydrogenase is found in the AD brain3; and (d) activation of calcium-dependent neural proteinase (calpain) is found in AD brains,163 which may trigger events leading to the formation of free radicals.164
The Contribution of Iron and Transition Metal Micronutrients to Diabetes and Metabolic Disease
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
Lipika Salaye, Zhenzhong Bai, Donald A. McClain
Systemic and cellular iron metabolism have been the subject of excellent recent reviews [9–11] and will be only briefly recapitulated here (Figure 15.1). Intestinal free ferric (Fe3+) iron is reduced to ferrous Fe2+ by duodenal cytochrome B (DCTB) and enters duodenal enterocytes by way of the divalent metal-ion transporter 1 (DMT1) and possibly other carriers. Dietary heme is directly absorbed into enterocytes, where iron is released by heme oxygenase (HMOX). Ferrous iron exits the enterocytes through the iron export channel ferroportin (FPN). After oxidization by hephaestin (HEPH), Fe3+ binds to transferrin (Tf) in the blood, which in turn binds to transferrin receptors (TfR) on the surface of target cells. In most cells (Figure 15.1, lower right), after endocytosis of TfR1 and acidification of the endosome, iron is released, reduced by STEAP (6-transmembrane epithelial antigen of the prostate), and enters the cytosol through DMT1, where it is used (e.g., for heme or Fe-S-cluster synthesis in mitochondria) or, if in excess, sequestered by ferritin. Apoferritin secreted into the circulation is a marker for tissue iron stores, although the trigger for its secretion versus use to sequester more iron is not known. The intracellular trafficking of iron is much more complicated than indicated in the figure. For example, iron is highly controlled and chaperoned to its various targets, as ferrous iron or after iron-sulfur cluster synthesis, by mechanisms that are still under study [6].
Iron metabolism and chronic inflammation in IgA nephropathy
Published in Renal Failure, 2023
Zhang-yu Tian, Zhi Li, Ling Chu, Yan Liu, Jin-rong He, Yu Xin, Ai-mei Li, Hao Zhang
Two functional isoforms of heme oxygenase exist in mammalian cells: HO-1 and HO-2. HO-2 is expressed in the brain, testis, cardiovascular and liver and can balance iron and redox metabolism as well as cellular messaging [158–160]. By contrast, HO-1 is a stress-inducible isozyme [161]. Under homeostatic conditions, HO-1 is constitutively expressed in iron-recycling macrophages in the spleen and liver and certain tolerogenic immune cells [162,163]. However, HO-1 is highly upregulated by most cells in response to free heme and many other pro-oxidants to provide protection against oxidative damage [140,141,164]. Micro and/or macroscopic hematuria is a typical symptom of IgAN that suggests potential induction of HO-1 in the glomeruli [165]. The HO-1 gene promoter length polymorphism was an important risk factor for mortality in IgAN [142].
Justicia carnea extracts ameliorated hepatocellular damage in streptozotocin-induced type 1 diabetic male rats via decrease in oxidative stress, inflammation and increasing other risk markers
Published in Biomarkers, 2023
John Adeolu Falode, Oluwaseun Igbekele Ajayi, Tolulope Victoria Isinkaye, Akinwunmi Oluwaseun Adeoye, Basiru Olaitan Ajiboye, Bartholomew I. C. Brai
Albuminuria is adversely and independently correlated with high bilirubin levels. Haem oxygenase catabolizes haem to produce bilirubin, which is expelled by liver cells (Ahn et al.2017). Previous research suggested that bilirubin is a harmful waste product (Han et al.2010) but it now appears to have antioxidant, anti-inflammatory and antiapoptotic effects (Wang et al.2016). Another research also stated that the likelihood of developing diabetic nephropathy is negatively correlated with serum total bilirubin levels. It was discovered that higher total bilirubin levels prevented diabetic nephropathy (Wang et al.2016). In this study, we discovered that type 1 diabetic animals receiving J. carnea treatment had considerably lower total and direct bilirubin levels than the diabetic groups. This implies that bilirubin levels that are lower could stop type 1 diabetes from developing.
Echinacoside alleviates osteoarthritis in rats by activating the Nrf2-HO-1 signaling pathway
Published in Immunopharmacology and Immunotoxicology, 2022
Nuclear factor E2-related factor 2 (Nrf2) is a pivotal transcription factor that balances oxidizing media and maintains the redox homeostasis of cells [14]. Nrf2 activated defense system mainly induces superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) [15]. Heme oxygenases (HOs) refer to enzymes that catalyze the decomposition of heme, mainly containing HO-1, heme oxygenase-2 (HO-2), and heme oxygenase-3 (HO-3) types [16]. Previous studies clarify that HO-1 participates in the defense mechanism against oxidative damage [17]. Crucially, accumulated evidence suggests that the Nrf2/HO-1 pathway exerts a critical regulatory role in OA. For instance, the inactivation of the Nrf2/HO-1 pathway leads to elevated activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and further aggravates OA [18]; sinomenine represses IL-1β-induced inflammatory response and cartilage destruction by activating the Nrf2/HO-1 pathway in mouse chondrocytes, prompting that sinomenine is a novel drug for the OA treatment [19]. However, whether Ech exerts a protective function in OA through the Nrf2/HO-1 pathway is unknown.