Search results for HMOX1

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Reaction (16 results from a total of 16)

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-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-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).
Identifier: R-HSA-9759176
Species: Homo sapiens
Compartment: nucleoplasm, endoplasmic reticulum membrane
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 (Reichard et al, 2007; Ishii et al, 2002; reviewed in Baird and Yamamoto, 2020).
Identifier: R-HSA-9759137
Species: Homo sapiens
Compartment: nucleoplasm
The HMOX1 gene encodes heme oxygenase, which converts free heme into billiverden. HMOX1 activity is cytoprotective, as excess free heme promotes apoptosis (reviewed in Loboda et al, 2016; Waza et al, 2018). HMOX1 gene expression is regulated in part by the binding of heterodimers of NFE2L2 and small MAF proteins such as MAFK to the antioxidant response element in the promoter (Ishii et al, 2000; reviewed in Baird and Yamamoto, 2020).
Identifier: R-HSA-189398
Species: Homo sapiens
Compartment: cytosol, endoplasmic reticulum membrane
Heme oxygenases (HMOXs) cleaves the heme ring at the alpha-methene bridge to form bilverdin. This reaction forms the only endogenous source of carbon monoxide. HMOX1 is inducible and is thought to have an antioxidant role as it is activated in virtually all cell types and by many types of "oxidative stress" (Poss & Tonegawa 1997). HMOX1 forms dimers/oligomers in the endoplasmatic reticulum. This oligomerization is crucial for the stabilization and function of HMOX1 in the ER (Hwang et al. 2009). HMOX2 is non-inducible.
Identifier: R-HSA-9708558
Species: Homo sapiens
Compartment: cytosol, mitochondrion
Heme oxygenase 1 (HMOX1) expression increases dramatically in cytosolic and mitochondrial fractions of human alveolar (A549), or bronchial epithelial cells (Beas-2b) exposed to either heme, lipopolysaccharide, or cigarette smoke extract (CSE). Mitochondrial localization of HMOX1 is also observed in a primary culture of human small airway epithelial cells (Siebos et al, 2007).
Identifier: R-HSA-9708497
Species: Homo sapiens
Compartment: nucleoplasm, cytosol
The BACH1 gene produces the transcription regulator protein BACH1 which contains 736 amino acids and is 88% identical to its mouse homolog. It contains basic leucine zipper and BTB-zinc finger domains (which are directly involved in DNA binding for transcription regulation) (Blouin et al, 1999).

The let-7 microRNA (miRNA) plays important roles in human liver development and diseases such as hepatocellular carcinoma, liver fibrosis and hepatitis wherein oxidative stress accelerates the progression of these diseases. It directly acts on the 3'-UTR of BACH1 and negatively regulates expression of this protein, and thereby up-regulates heme oxygenase (HMOX1) gene expression (Hou et al, 2012).

miR-155 is one of the TNFα-inducible endothelial microRNAs that bind to the BACH1 mRNA. Increased HMOX1 expression in endothelial cells by TNFα results from miR-155-induced repression of BACH1 rather than direct induction of HMOX1 via NF-κB. miR-155 is cytoprotective during inflammation by elevating HMOX1 expression in endothelial cells (Pulkkinen et al, 2011).

The microRNA miR‐196 directly acts on the 3′‐UTR of BACH1 messenger RNA and translationally represses the expression of this protein, and up‐regulates HMOX1 (Hou et al, 2010).
Identifier: R-HSA-9707523
Species: Homo sapiens
Compartment: nucleoplasm
Heme binds to four cysteine-proline motifs in the C-terminal region of BACH1 and inhibits the DNA-binding activity of BACH1-MAFK heterodimers resulting in HMOX1 induction. MAFK separates from the complex, and heme recruits nuclear exporters for BACH1 (Yoshida et al, 1988; Ogawa et al, 2001; Suzuki et al, 2004).
Identifier: R-HSA-9708557
Species: Homo sapiens
Compartment: nucleoplasm
The leucine-rich repeat family of F-box proteins (FBXLs) function as adapter for the SKP1-CUL1-F-box protein (SCF) E3 ubiquitin ligase. FBXL17 is a regulator of the nuclear factor erythroid 2-related factor 2 (NFE2L2) oxidative stress pathway. By binding to the transcriptional repressor/regulator protein BACH1 it controls the transcription of the NFE2L2 target heme oxygenase 1 (HMOX1) via turnover of BACH1 in the absence or presence of extrinsic oxidative stress (Tan et al, 2013).
Identifier: R-HSA-9708517
Species: Homo sapiens
Compartment: nucleoplasm
The leucine-rich repeat family of F-box proteins (FBXLs) function as adapter for the SKP1-CUL1-F-box protein (SCF) E3 ubiquitin ligase. FBXL17 is a regulator of the nuclear factor erythroid 2-related factor 2 (NFE2L2) oxidative stress pathway. By binding to the transcriptional repressor/regulator protein BACH1 it controls the transcription of the NFE2L2 target heme oxygenase 1 (HMOX1) via turnover of BACH1 in the absence or presence of extrinsic oxidative stress (Tan et al, 2013).
Identifier: R-HSA-9708525
Species: Homo sapiens
Compartment: nucleoplasm
The leucine-rich repeat family of F-box proteins (FBXLs) function as adapter for the SKP1-CUL1-F-box protein (SCF) E3 ubiquitin ligase. FBXL17 is a regulator of the nuclear factor erythroid 2-related factor 2 (NFE2L2) oxidative stress pathway. By binding to the transcriptional repressor/regulator protein BACH1 it controls the transcription of the NFE2L2 target heme oxygenase 1 (HMOX1) via turnover of BACH1 in the absence or presence of extrinsic oxidative stress (Tan et al, 2013).
Identifier: R-HSA-1250272
Species: Homo sapiens
Compartment: cytosol
Thioredoxin-interacting protein (TXNIP) binds NLRP3. Reactive oxygen species (ROS) such as H2O2 increase this interaction, while the ROS inhibitor APDC blocks it (Zhou et al. 2010). This interaction is proposed to activate the NLRP3 inflammasome.

Heme oxygenase (HMOX1), besides its enzymatic activity of the dimeric membrane protein isoform, also occurs as soluble cytosolic protein. It is probably this form that binds to the NACHT domain of NLRP3, suppressing production of epithelial cell-derived cytokines induced by activation of the NLRP3 inflammasome, and protecting airway epithelium in asthma (Lv et al, 2018).
Identifier: R-HSA-9709918
Species: Homo sapiens
Compartment: cytosol
In humans, activated PTK6 (BRK) phosphorylates STAT3 on tyrosine residue Y705. PTK6-mediated phosphorylation of STAT3 is promoted by STAP2 and inhibited by SOCS3 (Liu et al. 2006, Ikeda et al. 2010).

In mouse, Ptk6-mediated phosphorylation of Stat3 is promoted by Stap2 and inhibited by Socs3. Heme oxygenase-1 (Hmox1) binds to tyrosine-705 and three domains on Stat3 (DNA-binding, linker, and transactivation domains), directly regulating Stat3 activation. Additionally it 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 (Lin et al, 2020; Lin et al, 2017).
Identifier: R-HSA-9712274
Species: Homo sapiens
Compartment: cytosol
KEAP1:CUL3:RBX1-mediated degradation of NFE2L2 is relieved in the presence of oxidative or electrophilic stress, allowing NFE2L2 to translocate to the nucleus to support expression of target genes. NFE2L2 'inducers' are a varied group of endogenous and extracellular chemicals, including a number of pharmaceutical compounds approved for clinical use (reviewed in Cuadrado, 2019; Baird and Yamamoto, 2020). The mechanism by which NFE2L2:KEAP1 complex senses the oxidative stress and triggers NFE2L2 nuclear localization is unclear. It has been proposed that KEAP1, which is rich in reactive cysteines, may directly sense the oxidative stress via thiol modification and undergo conformational changes that stabilize NFE2L2 (Itoh et al. 1999). The reactive cysteine residues within KEAP1 undergo oxidation and form an intramolecular disulfide bond. Human KEAP1 has 27 cysteine residues and among those C257, C273, C288 and C297 are most reactive and can be oxidized. C273 of one KEAP1 molecule probably forms an intermolecular disulfide bridge with C288 of a second KEAP1 molecule (Zhang & Hannink 2003, Wakabayashi et al. 2004; reviewed in Baird and Yamamoto, 2020). Different NFE2L2 inducers can be grouped on the basis of which KEAP1 cysteine residues are involved in mediating their response (reviewed in Baird and Yamamoto, 2020). NFE2L2 inducers (e.g. sulforaphane, fumarates, and their derivatives) block ubiquitination of NFE2L2 by binding more or less irreversibly to L-cysteine 151 and other cysteine residues of KEAP1 (Brennan et al, 2015; Hu et al, 2011; Unni et al, 2020; Zhu et al, 2019). This strongly enhances induction of expression of all genes with antioxidant response elements (ARE), including HMOX1 and NQO1, among many others (Hong et al, 2005; reviewed in Baird and Yamamoto, 2020).

Sulforaphane has proved to be an effective chemoprotective agent in cell culture, carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer (Clarke et al, 2008). These preclinical studies demonstrate chemopreventive mode of actions of isothiocyanates, mainly related to a) detoxification (induction of phase II enzymes), b) anti-inflammatory properties by down-regulation of NFkappaB activity, c) cyclin-mediated cell cycle arrest and d) epigenetic modulation by inhibition of histone deacetylase activity. First prospective clinical trials were promising in patients with risk of prostate cancer recurrence (Gründemann and Huber, 2018; Kamal et al, 2020)

In cancer treatment, sulforaphane exhibited promising inhibitory effects on breast cancer, lung cancer, liver cancer, and other malignant tumors (Wu et al, 2020)

Five clinical trials showed a significant positive correlation between sulforaphane use and autism spectrum disorder (ASD) behavior and cognitive function. The current evidence shows with minimal side effects observed that sulforaphane appears to be a safe and effective treatment option for ASD (McGuinness and Kim, 2020).

Dimethyl fumarate (DMF) was effective in reducing the proportion of patients with MS relapse at 2 years (primary endpoint of DEFINE) and the annualized relapse rate (primary endpoint of CONFIRM) compared with placebo, with reduced disability progression also observed with the drug versus placebo in DEFINE. Dimethyl fumarate also reduced disease activity measures relative to placebo in these trials (Burness and Deeks, 2014; Xu et al, 2015). DMF is completely metabolized to monomethyl fumarate (MMF), and by giving it directly the usually mild side effects are alleviated further (Wynn et al, 2020).

Sulforaphane and dimethyl fumarate show IFN-independent antiviral activity. Both inhibit SARS-CoV-2 replication in vitro. Sulforaphane also inhibits seasonal coronavirus HCoV-OC43 (Olagnier et al, 2020; Ordonez et al, 2021).
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