Search results for HMOX1

Showing 17 results out of 27

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Protein (4 results from a total of 4)

Identifier: R-HSA-189395
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane
Primary external reference: UniProt: HMOX1: P09601
Identifier: R-HSA-9708524
Species: Homo sapiens
Compartment: mitochondrial outer membrane
Primary external reference: UniProt: HMOX1: P09601
Identifier: R-HSA-9609901
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: P09601
Identifier: R-HSA-9708567
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: P09601

Reaction (4 results from a total of 14)

Identifier: R-HSA-9707645
Species: Homo sapiens
Compartment: nucleoplasm, endoplasmic reticulum membrane
Transcription regulator protein BACH1 is a critical physiological repressor of heme oxygenase 1 (HMOX1). BACH1 binds to the multiple Maf recognition elements (MAREs) of HMOX1 enhancer MafK in vitro and represses its activity in vivo. BACH1 is inducible by hypoxia and IFN-gamma (Kitamuro et al, 2003; Sun et al, 2002).

NFE2L2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that activates transcription of a battery of cytoprotective genes by binding to the ARE (antioxidant response element). It is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. HMOX1 is one of the genes whose expression it activates (Huang et al, 2000; Reichard et al, 2007).
Identifier: R-HSA-6797268
Species: Homo sapiens
Compartment: nucleoplasm, endoplasmic reticulum membrane
In human peripheral blood monocytes Interleukin-4 (IL4) and IL13 significantly upregulate the levels of proteins involved in inflammatory resolution, including the ER membrane protein 15-lipoxygenase (ALOX15) (Chaitidis et al. 2005).
Identifier: R-HSA-9708536
Species: Homo sapiens
Compartment: cytosol, nucleoplasm
After exposure to hypoxia and heme or heme/hemopexin, soluble heme oxygenase 1 (HMOX1) is detected in the nucleus. Nuclear localization is also associated with reduction of HMOX1 activity. HMOX1 protein, whether it s enzymatically active or not, mediates activation of oxidant-responsive transcription factors, including activator protein-1 (AP-1). Nevertheless, nuclear HMOX1 protects cells against hydrogen peroxide-mediated injury equally as well as cytoplasmic HMOX1 (Lin et al, 2007).
Identifier: R-HSA-9708457
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane, cytosol
Cleavage of heme oxygenase 1 (HMOX1) by HM13 (Signal peptide peptidase) takes place in the ER membrane and removes the membrane domain from HMOX1, making it soluble in the cytosol. The reaction only occurs under conditions of hypoxia (Schaefer et al, 2017; Boname et al, 2014).

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-6789487
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000100292

Pathway (4 results from a total of 4)

Identifier: R-HSA-9707564
Species: Homo sapiens
Expression of heme oxygenase 1 (HMOX1) is regulated by various indicators of cell stress, while HMOX2 is expressed constitutively. Both catalyze the breakdown of heme into biliverdin (BV), carbon monoxide (CO), and ferrous iron. Biliverdin is immediately reduced to bilirubin (BIL). Both bilirubin and carbon monoxide can localize to different compartments and outside the cell. Cytoprotection by HMOX1 is exerted directly by HMOX1 and by the antioxidant metabolites produced through the degradation of heme. Additionally, due to the reactive nature of labile heme, its degradation is intrinsically protective.

HMOX1 confers cytoprotection against cell death in various models of lung and vascular injury by inhibiting apoptosis, inflammation, and immune cell proliferation. It binds to the NACHT domain of NLRP3 inflammasome, blocking its activation. In mouse it directly binds STAT3 to control the generation of pathogenic Th17 cells during neutrophilic airway inflammation. It also blocks phosphorylation of STAT3 by PTK6 and co-inhibits Socs3, a negative feedback factor of Stat3 activation, as well as RORγt, thereby decreasing Th2 and Th17 immune responses, and alleviating airway inflammation.

The beneficial effects of the three products generated by HMOX1 differ not only in their inherent molecular mechanisms, but also in their downstream cellular targets. To date, this is the only enzymatic system known to exhibit such characteristics. Iron is a vital component of many biological systems and is capable of producing hydroxyl radicals via fenton chemistry. For this reason, iron is sequestered by the storage multimer ferritin and to prevent oxidative damage while maintaining the iron pool. On the other hand, the protective effects of bilirubin and CO are broadly recognized, which has led to their consideration as therapeutics for a range of diseases. Bilirubin has been recognized as one of the most potent antioxidants in nature, and moderate increases of its serum level have been shown in numerous large-scale population and epidemiological studies to have a protective effect against cardiovascular and metabolic disease. These effects are mediated by bilirubin scavenging of superoxide anions and reactive nitrogen species (RNS), and by activating the transcription factor PPAR-alpha.

CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. CO possesses intriguing signaling properties affecting numerous critical cellular functions including but not limited to inflammation, cellular proliferation, and apoptotic cell death. Binding of CO with key ferrous hemoproteins serves as a posttranslational modification that regulates important processes as diverse as aerobic metabolism, oxidative stress, and mitochondrial bioenergetics. The most important of these is the mitochondrial cytochrome c oxidase (Cco). By locally blocking mitochondrial respiration the main source of reactive oxygen species (ROS) in the cell is switched off. Additionally CO enables efficient reduction of methemoglobin (MetHb) by H2O2, thus preventing the generation of free heme in hemorrhagic diseases and malaria (Origassa and Câmara, 2013; Morse et al, 2009; Ryter et al, 2006; Cooper and Brown, 2008; Hinds and Stec, 2008).
Identifier: R-HSA-9707587
Species: Homo sapiens
Heme oxygenase 1 (HMOX1) is regulated at the level of gene transcription, mRNA translation, localization and degradation. Its gene is often activated under a wide range of stressful conditions. The transcriptional control of HMOX1 is determined by inducible regulatory elements localized in the 5′ region of the promoter, so called antioxidant response elements (ARE)(Raghunath et al, 2018).

AREs on the HMOX1 gene are ultimately controlled by the enhancing NFE2L2:MAFK dimer and the repressing BACH1:MAFK dimer, both of which are influenced by a multitude of processes. Less specific enhancement occurs via AP-1 (FOS:JUN) dimers (Funes et al, 2020).

HMOX1 activity depends on dimerization in the ER membrane. Its membrane localization is abandoned by cleavage of the membrane domain by HM13. The resulting soluble enzyme is found in the cytosol, mitochondria, and the nucleus (Schaefer et al, 2017).
Identifier: R-HSA-9711123
Species: Homo sapiens
Cells are equipped with versatile physiological stress responses to prevent hazardous consequences resulting from exposure to chemical insults of endogenous and exogenous origin. Even at equitoxic doses, different stressors induce distinctive and complex signaling cascades. The responses typically follow cell perturbations at the subcellular organelle level.

Expression of heme oxygenase 1 (HMOX1) is regulated by various indicators of cell stress. Cytoprotection by HMOX1 is exerted directly by HMOX1 and by the antioxidant metabolites it produces through the degradation of heme.

Reactive oxygen and nitrogen species (RONS) are important mediators of chemical stress, as they are produced endogenously in mitochondria, and also result from redox activities of many toxins and heavy metal cations. The points of RONS action in the cell are plasma and ER membrane lipids, as well as DNA, both acting as sensors for the cellular response. On the other hand, chemotherapeutic agents exert their action via generation of RONS and induction of cancer cell apoptosis, while drug resistance associates with RONS-induced cancer cell survival (Sampadi et al, 2020; Moldogazieva et al, 2018).
Identifier: R-HSA-9707616
Species: Homo sapiens
Compartment: cytosol, extracellular region, nuclear envelope, nucleoplasm, plasma membrane
Extracellular hemoglobin, a byproduct of hemolysis, can release its prosthetic heme groups upon oxidation. Blood plasma contains proteins that scavenge heme. It is estimated that about 2–8% of the heme released in plasma becomes ‘bioavailable’, being internalized by bystander cells. If the heme degradation capacity of a cell, represented by heme oxidase 1 and 2, cannot be ramped up sufficiently then heme signaling and reactivity puts cells under stress. Platelets are activated by heme, and macrophages switch to the inflammatory type (Donegan et al, 2019; Gouveia et al, 2019).

Free (labile) heme accumulates in the blood stream in great amounts under pathological conditions like viral infections and malaria, but also ARDS amd COPD. The locally affected cells' primary reaction is to upregulate heme oxidase 1 (HMOX1) expression. HMOX1 induction in these cells not only removes heme from circulation but also triggers a functional switch toward the anti-inflammatory phenotype (Vijayan et al, 2018). However, heme scavenging and degradation systems may get overwhelmed by the sheer amount of heme present.

Heme promotes platelet activation, complement activation, vasculitis, and thrombosis (Bourne et al, 2020; Merle et al, 2018). Heme was recognized to act as a danger signal, damage-associated molecular pattern (DAMP), or alarmin (Soares and Bozza, 2016) and was shown to activate Toll-like receptor 4 (TLR4) signaling (Figueiredo et al, 2007; Janciauskiene et al, 2020). It also has a role as corepressor in the circadian clock system (Ko and Takahashi, 2006). BACH1 is regulated by heme in a cell, thus placing heme as a signaling molecule in gene expression in higher eukaryotes. The regulation of BACH1 by heme may be important for the stress response in general (Suzuki et al, 2004).

Extracellular hemoglobin, a byproduct of hemolysis, can release its prosthetic heme groups uponoxidation. Due to the reactive nature of free heme, the blood plasma contains proteins that scavenge heme. It is estimated that about 2–8% of the heme released in plasma becomes ‘bioavailable’, being internalized by bystander cells. Failure of nearby cells to sufficientlymetabolize free heme can incite platelet activation, macrophage differentiation, and oxidative stress (Donegan et al, 2019; Gouveia et al, 2019).

Complex (2 results from a total of 2)

Identifier: R-HSA-9706826
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane
Identifier: R-HSA-9708921
Species: Homo sapiens
Compartment: mitochondrial outer membrane

Set (1 results from a total of 1)

Identifier: R-HSA-189382
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane

Icon (1 results from a total of 1)

Species: Homo sapiens
Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin
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