Heme iron

BACKGROUND: RBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits a preconditioning response through activation of antioxidant, anti-inflammatory, and iron-scavenging pathways, as measured by heme oxygenase-1 (HO-1), interleukin-10 (IL-10), and ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely and effectively elicit a preconditioning response in patients undergoing cardiac surgery. METHODS: This phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted in 19 centres across the USA, Canada, and Australia, enrolled patients scheduled to undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve surgery with cardiopulmonary bypass...

Heme degradation by the heme oxygenase (HMOX) family of enzymes is critical for maintaining homeostasis and limiting heme-induced tissue damage. Macrophages express HMOX1 and 2 and are critical sites of heme degradation in healthy and diseased states. Here we review the functions of the macrophage heme oxygenase system and its clinical relevance in discrete groups of pathologies where heme has been demonstrated to play a driving role. HMOX1 function in macrophages is essential for limiting oxidative tissue damage in both acute and chronic hemolytic disorders...

Non-alcoholic fatty liver disease (NAFLD) has gradually become the most prevalent chronic liver disease in the world, but its pathogenesis has not been fully elucidated. Ferroptosis is a novel type of programmed cell death caused by iron-dependent lipid peroxidation. Heme oxygenase-1 is a recognized antioxidant enzyme and an important regulatory factor in ferroptosis that modulates ferroptosis through various pathways and, in turn, regulates NAFLD. This paper reviews the regulatory mechanism of heme oxygenase-1 on NAFLD in ferroptosis pathway, with a view to clarifying the occurrence and development mechanisms of NAFLD and providing new vision and targets for its prevention and treatment...

Heme biosynthesis in the Gram-positive bacteria occurs mostly via a pathway that is distinct from that of eukaryotes and Gram-negative bacteria in the three terminal heme synthesis steps. In many of these bacteria heme is a necessary cofactor that fulfills roles in respiration, gas sensing, and detoxification of reactive oxygen species. These varying roles for heme, the requirement of iron and glutamate, as glutamyl tRNA, for synthesis, and the sharing of intermediates with the synthesis of other porphyrin derivatives necessitates the need for many points of regulation in response to nutrient availability and metabolic state...

l-Cysteine is a highly reactive amino acid that is modified into a variety of chemical structures, including cysteine sulfinic acid in human metabolic pathways, and sulfur-containing scaffolds of amino acids, alkaloids, and peptides in natural product biosynthesis. Among the modification enzymes responsible for these cysteine-derived compounds, metalloenzymes constitute an important family of enzymes that catalyze a wide variety of reactions. Therefore, understanding their reaction mechanisms is important for the biosynthetic production of cysteine-derived natural products...

Ferroptosis, an iron-dependent regulated cell death caused by excessive lipid peroxide accumulation, has emerged as a promising therapeutic target in various cancers, including non-small cell lung cancer (NSCLC). In this study, we identified the long non-coding RNA RGMB-AS1 as a key regulator of ferroptosis in NSCLC. Mechanistically, RGMB-AS1 interacted with heme oxygenase 1 (HMOX1) and prevented its ubiquitination by the E3 ligase TRC8, leading to increased HMOX1 stability and enhanced ferroptosis. Additionally, RGMB-AS1 bound to the 82-87 amino acid region of N-alpha-acetyltransferase 10 (NAA10), stimulating its acetyltransferase activity and promoting the conversion of acetyl-CoA to HMG-CoA, further contributing to ferroptosis...

Chronic liver diseases are complications of thalassemia with iron overload. Iron chelators are required to remove excessive iron, and antioxidants are supplemented to diminish harmful reactive oxygen species (ROS), purposing to ameliorate oxidative liver damage and dysfunctions. The deferiprone-resveratrol hybrid (DFP-RVT) is a synthetic iron chelator possessing anti-β-amyloid peptide aggregation, anti-malarial activity, and hepatoprotection in plasmodium-infected mice. The study focuses on investigating the antioxidant, cytotoxicity, iron-chelating, anti-lipid peroxidation, and antioxidant defense properties of DFP-RVT in iron-loaded human hepatocellular carcinoma (Huh7) cells...

The process of heme binding to a protein is prevalent in almost all forms of life to control many important biological properties, such as O2 -binding, electron transfer, gas sensing or to build catalytic power. In these cases, heme typically binds tightly (irreversibly) to a protein in a discrete heme binding pocket, with one or two heme ligands provided most commonly to the heme iron by His, Cys or Tyr residues. Heme binding can also be used as a regulatory mechanism, for example in transcriptional regulation or ion channel control...

ETHNOPHARMACOLOGICAL RELEVANCE: Cortex fraxini (also known as Qinpi), the bark of Fraxinus rhynchophylla Hance and Fraxinus stylosa Lingelsh, constitutes a crucial component in several traditional Chinese formulas (e.g., Baitouweng Tang, Jinxiao Formula, etc.) and has demonstrated efficacy in alleviating intestinal carbuncle and managing diarrhea. Cortex fraxini has demonstrated commendable anticancer activity in the realm of Chinese ethnopharmacology; nevertheless, the underlying mechanisms against colorectal cancer (CRC) remain elusive...

Iron deficiency (ID) is a common and challenging problem in adolescence. In order to prevent, recognize, and treat ID in this age range, it is critical to understand the recommended daily intake of iron in relation to an adolescent's activity, dietary habits, and basal iron losses. Adolescents following vegetarian or vegan diets exclusively rely on plant based, non-heme iron which has decreased bioavailability compared to heme iron and requires increased total iron intake. Individuals with disordered eating habits, excessive menstrual blood loss, and certain chronic health conditions (including inflammatory bowel disease and heart failure) are at high risk of ID and the development of symptomatic iron deficiency anemia (IDA)...

Ovarian clear cell carcinoma (OCCC) is a unique clinicopathological subtype of epithelial ovarian cancer that is resistant to standard chemotherapy. Eribulin, a microtubule dynamics inhibitor of halichondrin class, has unique effects in the cancer microenvironment such as induction of epithelization and reduction in metastatic potential in breast cancer cells; however, nothing is known about the effect of eribulin and the detailed mechanisms in OCCC. This study aimed to investigate the involvement of ferroptosis and its mechanism in the antitumor activity of eribulin in OCCC cells and a mouse xenograft model...

Heme is a coordination complex formed by the binding of iron ions and porphyrin rings. Its metabolic processes are associated with various cancers, including gastric cancer (GC). In recent years, long non-coding RNAs (LncRNAs) have been identified as key regulatory factors in GC. However, the role of LncRNAs associated with heme metabolism in GC and their relationship with prognosis have not been reported. In this study, we constructed a novel LncRNA signature related to heme metabolism (HMlncSig) and validated its prognostic value for predicting the survival of GC patients through training, testing, and validation cohorts...

BACKGROUND: The International Agency for Research on Cancer classified processed meats (PMs) as "carcinogenic" and red meat as "probably carcinogenic" for humans. The possible relationship between colorectal cancer (CRC) risk and the mechanisms involved in the carcinogenesis of PMs have not been established yet. Nitrosyl-heme and heme iron have been proposed as potential-related compounds. The aim of this study was to determine the association between nitrosyl-heme and heme iron intake and CRC risk among participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain study...

BACKGROUND: Total iron (TI) intake and differentiation between heme iron (HI) and nonheme iron (NHI) are uncommon despite markedly different bioavailability. OBJECTIVES: To create a database compiling information from studies that directly assessed the HI content of animal products using the Hornsey method, and to explore differences in estimates of HI intake between the data compiled and the Monsen method. METHODS: A literature search identified studies that chemically characterized the HI content of animal-based foods using the Hornsey method; HI, NHI, and TI contents (mg/100 g) were compiled...

BACKGROUND: The consumption of processed meats (PMs) and red meats are linked to the likelihood of developing colorectal cancer. Various theories have been proposed to explain this connection, focusing on nitrosyl-heme and heme iron intake. We hypothesized that differences in nitrosyl-heme and heme iron intakes will be associated with various sociodemographic and lifestyle factors. METHODS: The study included 38,471 healthy volunteers (62% females) from five Spanish regions within the EPIC-Spain cohort...

The lipoxygenases (LOXs) are non-heme iron-containing dioxygenases that play an important role in plant growth and defense responses. There is scarce knowledge regarding the LOX gene family members and their involvement in biotic and abiotic stresses in potato. In this study, a total of 17 gene family members (StLOXs) in potato were identified and clustered into three subfamilies: 9-LOX type I, 13-LOX type I, and 13-LOX type II, with eleven, one, and five members in each subfamily based on phylogenetic analysis...

Forty LW × L pigs (20 boars and 20 gilts) (51.1 ± 0.41 kg) were allocated to a 2 × 2 × 2 factorial design with the respective factors being supplemental organic iron (Fe, 0 and 500 mg/kg), inulin (In, 0 and 50 g/kg) and sex (boars and gilts). After 5 weeks the animals were transported to an abattoir before slaughter and collection of samples. Serum iron was increased by supplemental Fe (28.4 v. 30.9 μmol/L, P = 0...

In this study, the molecular mechanisms of iron transport and homeostasis regulated by the Antarctic krill-derived heptapeptide-iron (LVDDHFL-iron) complex were explored. LVDDHFL-iron significantly increased the hemoglobin, serum iron, total iron binding capacity levels, and iron contents in the liver and spleen to normal levels, regulated the gene expressions of iron homeostasis, and enhanced in vivo antioxidant capacity in iron-deficiency anemia mice ( P < 0.05). The results revealed that iron ions within LVDDHFL-iron can be transported via the heme transporter and divalent metal transporter-1, and the absorption of LVDDHFL-iron involved receptor-mediated endocytosis...

Impact of high-pressure processing (HP-P) on hemolymph and lipid globular structures of the edible portion (EP) of blood clams (BC) was investigated. HP-P above 400 MPa decreased heme iron content, while upsurged non-heme iron content. Increasing pressure induced gaps and abnormal hemocyte cell arrangements. However, HP-P at 300 MPa improved and maintained total hemocyte counts, the heme iron content, and a*-value in BC-EP. For lipid globular structures, the mean diameter drastically decreased when an HP-P pressure of 600 MPa was employed...

Iron protoporphyrin IX (heme) is a redox-active cofactor that is bound in mammalian cells by GAPDH and allocated by a process influenced by physiologic levels of NO. This impacts the activity of many heme proteins including indoleamine dioxygenase-1 (IDO1), a redox enzyme involved in immune response and tumor growth. To gain further understanding we created a tetra-Cys human GAPDH reporter construct (TC-hGAPDH) which after labeling could indicate its heme binding by fluorescence quenching. When purified or expressed in a human cell line, TC-hGAPDH had properties like native GAPDH and heme binding quenched its fluorescence by 45-65%, allowing it to report on GAPDH binding of mitochondrially-generated heme in live cells in real time...