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Information on EC 1.14.14.18 - heme oxygenase (biliverdin-producing) and Organism(s) Mus musculus and UniProt Accession P14901
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1.14.14.18 heme oxygenase (biliverdin-producing)IUBMB Comments
This mammalian enzyme participates in the degradation of heme. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules . The third oxygen molecule provides the oxygen atom that converts the alpha-carbon to CO. The enzyme requires NAD(P)H and EC 1.6.2.4, NADPH---hemoprotein reductase. cf. EC 1.14.15.20, heme oxygenase (biliverdin-producing, ferredoxin).
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Word Map
- 1.14.14.18
- monoxide
-
cytoprotective
- endothelial
- necrosis
- dismutase
- protoporphyrin
-
erythroid
-
2-related
- tnf
- bilirubin
- artery
- malondialdehyde
- lipopolysaccharide
- catalase
- hemin
-
neuroprotective
- ischemia
- gsh
- lps
- sod
-
anti-oxidant
- mapks
- sirna
- caspase-3
- quinone
- pulmonary
-
reperfusion
-
lps-induced
- hypoxia
- cyclooxygenase-2
- cox-2
- ferritin
- erk
-
nf-e2-related
-
anti-apoptotic
- cobalt
- myeloperoxidase
-
ischemia-reperfusion
-
nrf2-mediated
-
pro-oxidant
-
kelch-like
-
nadph:quinone
-
factor-2
-
lps-stimulated
-
2-like
-
erythroid-derived
- oxygenases
-
delta-aminolevulinic
- sulforaphane
- hyperbilirubinemia
- medicine
- drug development
- analysis
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
heme oxygenase-1, heme oxygenase, hmox1, heme oxygenase 1, haem oxygenase, hsp32, heme oxygenase-2, hmox2, heme oxygenase 2, hmox1a, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
heme oxygenase-1
-
HO-1
-
haem oxygenase
-
-
-
-
heme oxygenase-1
-
-
HO-1
-
-
HO-2
ORP33 proteins
-
-
-
-
oxygenase, heme (decyclizing)
-
-
-
-
proteins, specific or class, ORP33 (oxygen-regulated protein 33,000-mol.-wt.)
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
SYSTEMATIC NAME
IUBMB Comments
protoheme,NADPH-hemoprotein reductase:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating)
This mammalian enzyme participates in the degradation of heme. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules [4]. The third oxygen molecule provides the oxygen atom that converts the alpha-carbon to CO. The enzyme requires NAD(P)H and EC 1.6.2.4, NADPH---hemoprotein reductase. cf. EC 1.14.15.20, heme oxygenase (biliverdin-producing, ferredoxin).
CAS REGISTRY NUMBER
COMMENTARY
9059-22-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized electron donor + H2O
-
-
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
-
-
-
-
?
protoheme + [reduced NADPH-hemoprotein reductase] + O2
biliverdin + Fe2+ + CO + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
endogenous HO-1 shows anti-apoptotic activity, and is overexpressed in various cancer diseases and might contribute to cancer progression
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 catalyzes the rate-limiting step of heme degradation and plays an important anti-inflammatory role via its enzymatic products carbon monoxide and biliverdin
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 gene is a glia-expressing wound-responsive gene, HO-1 gene expression associated with traumatic brain injury involving the toll-like receptor 2, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 is an antioxidant and cytoprotective enzyme. Methoxychalcones, especially 5-methoxychalcone, 3,4,5-trimethoxychalcone, and 3,4,5,3',4',5'-hexamethoxychalcone, induce the enzyme expression and activity in macrophages without causing cytotoxicity, they also cause anti-inflamatory affects, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 is an inducible enzyme that catalyzes the rate-limiting step in the degradation of heme to biliverdin, CO and iron
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 participates in the degradation of heme, the enzyme is involved in tumor development
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 shows anti-inflammatory effect, inhibition of HO-1 or scavenging of CO significantly reverses the inhibition of LPS-stimulated nitrite accumulation by tanshinone IIA, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 shows anti-inflammatory properties
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
statin-induced heme oxygenase-1 increases NF-kappaB activation and oxygen radical production in cultured neuronal cells exposed to lipopolysaccharide, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-1 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
the enzyme has anti-inflammatory activity and is involved in mediation of curcumin's inhibitory effect on inducible NO synthase expression and NO production. Treatment with HO inhibitor abolishes the inhibitory effect of curcumin on lipopolysaccharide-induced NF-kappaB activation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
the enzyme shows anti-inflammatory activity, HO-1 expression is induced via the ERK1/2 activation pathway
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
-
HO is a microsomal enzyme and catalyzes the oxidation of the alpha-meso-carbon bridge of heme moieties resulting in the generation of ferrous iron, carbon monoxide and biliverdin. HO-1 is inducible and plays a main role in the cellular oxidant/antioxidant balance, whereas HO-2 is constitutive and involved in the physiologicalmetabolism of heme
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
-
HO-1 is the rate-limiting enzyme in heme degradation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-2 and its reaction products, detailed overview
-
-
?
additional information
?
-
inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice. Downmodulation of HO-1 by siRNA resulted in increased cellular damage and apoptosis, reduced proliferation, reduced growth of orthotopic hepatocellular carcinoma and reduced angiogenesis, mechanism, overview
-
-
?
additional information
?
-
-
inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice. Downmodulation of HO-1 by siRNA resulted in increased cellular damage and apoptosis, reduced proliferation, reduced growth of orthotopic hepatocellular carcinoma and reduced angiogenesis, mechanism, overview
-
-
?
additional information
?
-
LPS-induced maturation of dendritic cells is dependent on STAT3 phosphorylation and independent of HO-1 activity, overview
-
-
?
additional information
?
-
-
LPS-induced maturation of dendritic cells is dependent on STAT3 phosphorylation and independent of HO-1 activity, overview
-
-
?
additional information
?
-
overexpression of HO-1 in B16F10 cells confers resistance to cisplatin treatment, overview
-
-
?
additional information
?
-
-
overexpression of HO-1 in B16F10 cells confers resistance to cisplatin treatment, overview
-
-
?
additional information
?
-
PMA-dependent activation of HO-1 is mediated via a nonclassical NF-kappaB pathway that is independent of IKK2 activity
-
-
?
additional information
?
-
the anti-inflammatory activity of Phellinus linteus is mediated through the PKCdelta/Nrf2/ARE signaling to up-regulation of heme oxygenase-1
-
-
?
additional information
?
-
-
hemoglobin neurotoxicity is attenuated by inhibitors of the protein kinase CK2 and protein kinase C independent of heme oxygenase activity
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
protoheme + [reduced NADPH-hemoprotein reductase] + O2
biliverdin + Fe2+ + CO + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
endogenous HO-1 shows anti-apoptotic activity, and is overexpressed in various cancer diseases and might contribute to cancer progression
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 catalyzes the rate-limiting step of heme degradation and plays an important anti-inflammatory role via its enzymatic products carbon monoxide and biliverdin
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 gene is a glia-expressing wound-responsive gene, HO-1 gene expression associated with traumatic brain injury involving the toll-like receptor 2, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 is an antioxidant and cytoprotective enzyme. Methoxychalcones, especially 5-methoxychalcone, 3,4,5-trimethoxychalcone, and 3,4,5,3',4',5'-hexamethoxychalcone, induce the enzyme expression and activity in macrophages without causing cytotoxicity, they also cause anti-inflamatory affects, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 is an inducible enzyme that catalyzes the rate-limiting step in the degradation of heme to biliverdin, CO and iron
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 participates in the degradation of heme, the enzyme is involved in tumor development
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 shows anti-inflammatory effect, inhibition of HO-1 or scavenging of CO significantly reverses the inhibition of LPS-stimulated nitrite accumulation by tanshinone IIA, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
HO-1 shows anti-inflammatory properties
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
statin-induced heme oxygenase-1 increases NF-kappaB activation and oxygen radical production in cultured neuronal cells exposed to lipopolysaccharide, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-1 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
the enzyme has anti-inflammatory activity and is involved in mediation of curcumin's inhibitory effect on inducible NO synthase expression and NO production. Treatment with HO inhibitor abolishes the inhibitory effect of curcumin on lipopolysaccharide-induced NF-kappaB activation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
the enzyme shows anti-inflammatory activity, HO-1 expression is induced via the ERK1/2 activation pathway
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
-
HO is a microsomal enzyme and catalyzes the oxidation of the alpha-meso-carbon bridge of heme moieties resulting in the generation of ferrous iron, carbon monoxide and biliverdin. HO-1 is inducible and plays a main role in the cellular oxidant/antioxidant balance, whereas HO-2 is constitutive and involved in the physiologicalmetabolism of heme
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
-
HO-1 is the rate-limiting enzyme in heme degradation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-2 and its reaction products, detailed overview
-
-
?
additional information
?
-
inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice. Downmodulation of HO-1 by siRNA resulted in increased cellular damage and apoptosis, reduced proliferation, reduced growth of orthotopic hepatocellular carcinoma and reduced angiogenesis, mechanism, overview
-
-
?
additional information
?
-
-
inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice. Downmodulation of HO-1 by siRNA resulted in increased cellular damage and apoptosis, reduced proliferation, reduced growth of orthotopic hepatocellular carcinoma and reduced angiogenesis, mechanism, overview
-
-
?
additional information
?
-
LPS-induced maturation of dendritic cells is dependent on STAT3 phosphorylation and independent of HO-1 activity, overview
-
-
?
additional information
?
-
-
LPS-induced maturation of dendritic cells is dependent on STAT3 phosphorylation and independent of HO-1 activity, overview
-
-
?
additional information
?
-
overexpression of HO-1 in B16F10 cells confers resistance to cisplatin treatment, overview
-
-
?
additional information
?
-
-
overexpression of HO-1 in B16F10 cells confers resistance to cisplatin treatment, overview
-
-
?
additional information
?
-
PMA-dependent activation of HO-1 is mediated via a nonclassical NF-kappaB pathway that is independent of IKK2 activity
-
-
?
additional information
?
-
the anti-inflammatory activity of Phellinus linteus is mediated through the PKCdelta/Nrf2/ARE signaling to up-regulation of heme oxygenase-1
-
-
?
additional information
?
-
-
hemoglobin neurotoxicity is attenuated by inhibitors of the protein kinase CK2 and protein kinase C independent of heme oxygenase activity
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
zinc protoporphyrin IX
Zn(II)PPIX, a selective HO-1 inhibitor, Zn(II)PPIX exerts dose-dependent antitumor effects and shows retardation of tumor growth
-
FR180204
-
ERK inhibitor, reduces baseline culture HO activity, without altering the activity of recombinant HO-1 or HO-2
SL327
-
MEK inhibitor, reduces baseline culture HO activity, without altering the activity of recombinant HO-1 or HO-2
U0126
-
MEK inhibitor, reduces baseline culture HO activity, without altering the activity of recombinant HO-1 or HO-2
Zn(II) protoporphyrin IX
-
mitigates brazilin-induced activity of HO-1 and inhibition of NO, PEG2, TNF-alpha and IL-1beta production in lipopolysaccharide-stimulated RAW264.7 macrophages
zinc protoporphyrin IX
-
activity of both recombinant isoenzymes HO-1 and HO-2 is strongly inhibited
-
additional information
-
no inhibition by phosphatidylinositol 3-kinase inhibitors LY294002 and LY303511, by 4,5,6,7-tetrabromobenzotriazole, 2-dimethyl-amino-4,5,6,7-tetrabromo-1H-benzimidazole, and by the PKC inhibitor GF109203X
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
brazilin
-
main constituent of Caesalpinia sappan, induces HO-1 expression in a concentration-dependent manner at 0.01-0.3 mM at the level of protein synthesis, thus without affecting mRNA transcription of HO-1
additional information
at low concentrations curcumin induces the expression of HO-1 in RAW264.7 macrophages
-
additional information
cobalt protoporphyrin, CoPPIX, induces the enzyme, molecular mechanism, overview, CoPPIX inhibits STAT3 phosphorylation and the LPS-mediated maturation of bone marrow-derived dendritic cells independently of HO-1
-
additional information
-
cobalt protoporphyrin, CoPPIX, induces the enzyme, molecular mechanism, overview, CoPPIX inhibits STAT3 phosphorylation and the LPS-mediated maturation of bone marrow-derived dendritic cells independently of HO-1
-
additional information
lipopolysaccharide, from Escherichia coli, serotype 0127:B8, upregulates the expression of HO-1 in adult and fetal mouse liver, maternal LPS exposure results in oxidative stress in fetuses, which may contribute to LPS-induced developmental toxicity, LPS-induced upregulation of HO-1 is blocked by alpha-phenyl-N-t-butylnitrone, PBN, a free radical spin trapping agent, overview
-
additional information
-
lipopolysaccharide, from Escherichia coli, serotype 0127:B8, upregulates the expression of HO-1 in adult and fetal mouse liver, maternal LPS exposure results in oxidative stress in fetuses, which may contribute to LPS-induced developmental toxicity, LPS-induced upregulation of HO-1 is blocked by alpha-phenyl-N-t-butylnitrone, PBN, a free radical spin trapping agent, overview
-
additional information
methoxychalcones, especially 5-methoxychalcone, 3,4,5-trimethoxychalcone, and 3,4,5,3',4',5'-hexamethoxychalcone, induce the enzyme expression and activity in macrophages, overview, increase in heme oxygenase activity and HO-1 protein expression mediated by CH25 is significantly attenuated by the presence of an inhibitor of PI3K LY2940002, as well as by the addition of the glutathione precursor NAC
-
additional information
simvastatin induces the enzyme in neurons, HO-1 upregulation is significantly associated with increased nuclear factor kappa B activation, manifested as IkappaBalpha phosphorylation and p65 nuclear translocation, as well as increased production of superoxides, inhibition of the effects by zinc protoporphyrin
-
additional information
striatal blood injection increases HO activity, and oxidative stress induces the enzyme, overview
-
additional information
-
striatal blood injection increases HO activity, and oxidative stress induces the enzyme, overview
-
additional information
tanshinone IIA from Salvia miltiorrhiza induces heme oxygenase-1 expression via intracellular production of reactive oxygen species, and inhibits lipopolysaccharide-induced nitric oxide expression in RAW 264.7 cells. Inhibition of HO-1 or scavenging of CO significantly reverses the inhibition of LPS-stimulated nitrite accumulation by tanshinone IIA, signaling pathways, overview. Activation of PI 3-K and ERK signaling pathways are required for tanshinone-induction of HO-1 protein expression in RAW 264.7 macrophages
-
additional information
the HO-1 gene is transcriptionally induced by the phorbol ester PMA in cell cultures of monocytic cells with a regulatory pattern that is different from that of LPS-dependent HO-1 induction in these cells, overview, the upregulation is abrogated in embryonic fibroblasts from p65-/- mice, antioxidant N-acetylcysteine and inhibitors of p38 MAPK or serine/threonine kinase CK2 also block the upregulating effect of PMA, thus induction of HO-1 gene expression by PMA is regulated via an IkappaB kinase-independent, atypical NFkappaB pathway that is mediated via the activation of p38 MAPK and CK2, overview, PMA-dependent HO-1 gene activation requires IkappaBalpha, but notIKK2
-
additional information
the PKCdelta/Nrf2/ARE signaling up-regulates heme oxygenase-1
-
additional information
the toll-like receptor 2 is involved in HO-1 induction in glial cells, 34fold induction of HO-1 by stab-wound injury in wild-type mice, overview
-
additional information
-
the toll-like receptor 2 is involved in HO-1 induction in glial cells, 34fold induction of HO-1 by stab-wound injury in wild-type mice, overview
-
additional information
tranilast, i.e. N-[3',4'-dimethoxycinnamonyl] anthranilic acid, an orally active anti-allergic drug, tranilast induces heme oxygenase-1 expression through the extracellular signal-regulated kinase-1/2 pathway in RAW264.7 macrophages. Effects of tranilast on LPS-induced PGE2, NO, TNF-alpha, and IL-1beta production are partially reversed by the HO-1 inhibitor tin protoporphyrin, overview. UO126 significantly inhibits tranilast-induced HO-1 expression, but neither SB203580 nor SP600125 have a significant effect on HO-1 expression by tranilast
-
additional information
-
gamma-irradition of 0.5 Gy/min dose power causes a significant increase of activity
-
additional information
-
hemin is an inducer of HO-1, additive effect of hemin with dexamethasone, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
full-length HO-1 is an integral membrane protein
-
in response to different stimuli, e.g. hypoxia by 3% oxygen or incubation with hemin or heme-hemopexin, HO-1 can migrate to the nucleus. Nuclear translocation is associated with truncation of the C-terminus of HO-1
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
isoform HO-1 modulates the function of transcriptional factor Nuclear factor erythroid 2-related factor 2 (Nrf2). In oxidative stress, nuclear isoform HO-1 interacts with Nrf2 and stabilizes it from glycogen synthase kinase 3beta-mediated phosphorylation coupled with ubiquitin-proteasomal degradation, thereby prolonging its accumulation in the nucleus
physiological function
additional information
-
in cells, Hmox1 or Nfe2l2 RNA silencing prevents IL-10 and IL-1Ra up-regulation, and HO-1 induction fails post-LPS in Nfe2l2-silenced cells and post-sepsis in Nfe2l2-/- mice
physiological function
-
mice lacking the HO-1 gene frequently die in utero, and the mice that survive to adulthood exhibit growth failure, anemia, chronic inflammation characterized by hepatosplenomegaly, leukocytosis, glomerulonephritis, and histological hepatoportal cellular infiltration. HO-1 serves to provide cytoprotection against oxidative stress and is necessary in mammals
physiological function
-
HO-1 together with dichloromethane induces interleukin-10 expression in liver. HO-1, acting through the Nfe2l2, i.e. Nrf2, transcription factor, links anti-inflammatory cytokine expression to activation of mitochondrial biogenesis. HO1 induction after LPS stimulates anti-inflammatory interleukin-10 and interleukin-1 receptor antagonist expression in mouse liver, human HepG2 cells, and mouse J774.1 macrophages but blunted tumor necrosis factor-alpha expression
physiological function
-
the enzyme exhibits protective effects on cecal ligation and puncture-induced acute lung injury via regulating cell surface thrombomodulin and activated protein C expression and modulating blood coagulation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). HMOX1_MOUSE
289
1
32929
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
construction of deletion and/or disruption mutants of HO-1, phenotypes, overview
additional information
construction of deletion and/or disruption mutants of HO-1, phenotypes, overview
additional information
HO-1 expression is reduced in toll-like receptor 2 TLR2-knockout mice after stab-wound injury, overview
additional information
-
HO-1 expression is reduced in toll-like receptor 2 TLR2-knockout mice after stab-wound injury, overview
additional information
inhibition of HO-1 expression by small interfering RNA decreases cellular survival and apoptosis in the mouse hepatoma cell lines Hepa129 and Hepa1-6, and orthotopic tumor growth in immune-competent C3H/HeN mice, mechanism. But application of siHO1 does not induce liver or kidney damage in mice, overview
additional information
-
inhibition of HO-1 expression by small interfering RNA decreases cellular survival and apoptosis in the mouse hepatoma cell lines Hepa129 and Hepa1-6, and orthotopic tumor growth in immune-competent C3H/HeN mice, mechanism. But application of siHO1 does not induce liver or kidney damage in mice, overview
additional information
knock-down of HO-1 expression by siRNA expression, overexpression of HO-1 in B16F10 cells confers resistance to cisplatin treatment, overview
additional information
-
knock-down of HO-1 expression by siRNA expression, overexpression of HO-1 in B16F10 cells confers resistance to cisplatin treatment, overview
additional information
RNA interference with HO-1 siRNA reduces the expression of HO-1 transcripts and protein as well as oxygen radical production
additional information
construction of deletion and/or disruption mutants of HO-2, phenotypes, overview
additional information
construction of deletion and/or disruption mutants of HO-2, phenotypes, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of the kappaB element of the proximal rat HO-1 gene promoter region, -284 to -275, a nuclear target for the NF-kappaB subunit p65/RelA, expression in in RAW264.7 monocytes fused to the luciferase gene. HO-1 promoter activity is induced by p65, an NF-kappaB subunit, which is also termed RelA, and which is a member of the Rel family of proteins and is activated in response to a variety of stimuli
sense and antisense constructs, expression analysis in dendritic cells of different maturation levels, cobalt protoporphyrin leads to overexpression of HO-1, molecular mechanism, overview
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
cell treatment with Salvia plebeia methanolic extract significantly induces the expression of hemeoxygenase-1
-
HO-1 induction after hemoglobin treatment is decreased by about half by MEK inhibitors U0126 and SL327, and is completely prevented by the direct ERK inhibitor FR180204
-
HO-1 induction by hemoglobin. In cultures treated with hemoglobin plus dimethylsulfoxide vehicle for 4 h, which is a time point prior to the onset of neuronal lysis, HO-1 expression is increased 2.2fold over control cultures treated with vehicle only
-
HO-1 is induced by inflammation associated both with an anti-inflammatory response and with mitochondrial biogenesis
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
glial HO-1 expression might be an early marker of non-hemorrhagic cell injury in the striatum, time course of induction, overview
medicine
-
reduction in HO activity may contribute to the protective effect of MEK and ERK inhibitors against heme-mediated neuronal injury
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Han, Y.; Platonov, A.G.; Akhalaia, M.I.a.; Akhalaia, M.Y.; Song, J.Y.; Ahn, J.Y.; Yun, Y.S.
Tissue-specific changes in heme oxygenase activity and level of nonprotein thiols in C57Bl/6 mice after whole-body gamma-irradiation
Bull. Exp. Biol. Med.
140
341-344
2005
Mus musculus
McDaid, J.; Yamashita, K.; Chora, A.; Ollinger, R.; Strom, T.B.; Li, X.C.; Bach, F.H.; Soares, M.P.
Heme oxygenase-1 modulates the allo-immune response by promoting activation-induced cell death of T cells
FASEB J.
19
458-480
2005
Mus musculus
Hirai, K.; Sasahira, T.; Ohmori, H.; Fujii, K.; Kuniyasu, H.
Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice
Int. J. Cancer
120
500-505
2007
Mus musculus
Pae, H.O.; Jeong, S.O.; Koo, B.S.; Ha, H.Y.; Lee, K.M.; Chung, H.T.
Tranilast, an orally active anti-allergic drug, up-regulates the anti-inflammatory heme oxygenase-1 expression but down-regulates the pro-inflammatory cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW264.7 macrophages
Biochem. Biophys. Res. Commun.
371
361-365
2008
Mus musculus (P14901)
Kim, K.M.; Pae, H.O.; Zhung, M.; Ha, H.Y.; Ha, Y.A.; Chai, K.Y.; Cheong, Y.K.; Kim, J.M.; Chung, H.T.
Involvement of anti-inflammatory heme oxygenase-1 in the inhibitory effect of curcumin on the expression of pro-inflammatory inducible nitric oxide synthase in RAW264.7 macrophages
Biomed. Pharmacother.
62
630-636
2008
Mus musculus (P14901)
Nowis, D.; Bugajski, M.; Winiarska, M.; Bil, J.; Szokalska, A.; Salwa, P.; Issat, T.; Was, H.; Jozkowicz, A.; Dulak, J.; Stoklosa, T.; Golab, J.
Zinc protoporphyrin IX, a heme oxygenase-1 inhibitor, demonstrates potent antitumor effects but is unable to potentiate antitumor effects of chemotherapeutics in mice
BMC Cancer
8
197
2008
Homo sapiens (P09601), Homo sapiens, Mus musculus (P14901), Mus musculus
Kinobe, R.T.; Dercho, R.A.; Nakatsu, K.
Inhibitors of the heme oxygenase - carbon monoxide system: on the doorstep of the clinic?
Can. J. Physiol. Pharmacol.
86
577-599
2008
Mus musculus (O70252), Mus musculus (P14901), Homo sapiens (P09601), Homo sapiens (P30519)
Sawle, P.; Moulton, B.E.; Jarzykowska, M.; Green, C.J.; Foresti, R.; Fairlamb, I.J.; Motterlini, R.
Structure-activity relationships of methoxychalcones as inducers of heme oxygenase-1
Chem. Res. Toxicol.
21
1484-1494
2008
Mus musculus (P14901)
Chen-Roetling, J.; Li, Z.; Regan, R.F.
Hemoglobin neurotoxicity is attenuated by inhibitors of the protein kinase CK2 independent of heme oxygenase activity
Curr. Neurovasc. Res.
5
193-198
2008
Mus musculus
Gong, Q.; Yin, H.; Fang, M.; Xiang, Y.; Yuan, C.L.; Zheng, G.Y.; Yang, H.; Xiong, P.; Chen, G.; Gong, F.L.; Zheng, F.
Heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice
Int. Immunopharmacol.
8
792-798
2008
Mus musculus (P14901)
Sass, G.; Leukel, P.; Schmitz, V.; Raskopf, E.; Ocker, M.; Neureiter, D.; Meissnitzer, M.; Tasika, E.; Tannapfel, A.; Tiegs, G.
Inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice
Int. J. Cancer
123
1269-1277
2008
Mus musculus (P14901), Mus musculus, Mus musculus C3H/HEN (P14901)
Lin, Q.; Weis, S.; Yang, G.; Weng, Y.H.; Helston, R.; Rish, K.; Smith, A.; Bordner, J.; Polte, T.; Gaunitz, F.; Dennery, P.A.
Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress
J. Biol. Chem.
282
20621-20633
2007
Mus musculus, Rattus norvegicus (P06762)
Kim, B.C.; Jeon, W.K.; Hong, H.Y.; Jeon, K.B.; Hahn, J.H.; Kim, Y.M.; Numazawa, S.; Yosida, T.; Park, E.H.; Lim, C.J.
The anti-inflammatory activity of Phellinus linteus (Berk. & M.A. Curt.) is mediated through the PKCdelta/Nrf2/ARE signaling to up-regulation of heme oxygenase-1
J. Ethnopharmacol.
113
240-247
2007
Mus musculus (P14901)
Mashreghi, M.F.; Klemz, R.; Knosalla, I.S.; Gerstmayer, B.; Janssen, U.; Buelow, R.; Jozkowicz, A.; Dulak, J.; Volk, H.D.; Kotsch, K.
Inhibition of dendritic cell maturation and function is independent of heme oxygenase 1 but requires the activation of STAT3
J. Immunol.
180
7919-7930
2008
Mus musculus (P14901), Mus musculus, Mus musculus C57BL/6 (P14901)
Naidu, S.; Wijayanti, N.; Santoso, S.; Kietzmann, T.; Immenschuh, S.
An atypical NF-kappaB-regulated pathway mediates phorbol ester-dependent heme oxygenase-1 gene activation in monocytes
J. Immunol.
181
4113-4123
2008
Rattus norvegicus (P06762), Mus musculus (P14901)
Chen, M.; Regan, R.F.
Time course of increased heme oxygenase activity and expression after experimental intracerebral hemorrhage: correlation with oxidative injury
J. Neurochem.
103
2015-2021
2007
Mus musculus (P14901), Mus musculus
Chen, T.H.; Hsu, Y.T.; Chen, C.H.; Kao, S.H.; Lee, H.M.
Tanshinone IIA from Salvia miltiorrhiza induces heme oxygenase-1 expression and inhibits lipopolysaccharide-induced nitric oxide expression in RAW 264.7 cells
Mitochondrion
7
101-105
2007
Mus musculus (P14901)
Park, C.; Cho, I.H.; Kim, D.; Jo, E.K.; Choi, S.Y.; Oh, S.B.; Park, K.; Kim, J.S.; Lee, S.J.
Toll-like receptor 2 contributes to glial cell activation and heme oxygenase-1 expression in traumatic brain injury
Neurosci. Lett.
431
123-128
2008
Mus musculus (P14901), Mus musculus, Mus musculus C57BL/6 (P14901)
Mores, N.; Errico, S.; Pusateri, A.; Barone, E.; Mancuso, C.
Heme oxygenase expression and activity in immortalized hypothalamic neurons GT1-7
Neurosci. Lett.
444
106-108
2008
Mus musculus
Li, X.Y.; Zhang, C.; Wang, S.F.; Ji, Y.L.; Wang, H.; Zhao, L.; Xu, D.X.
Maternally administered lipopolysaccharide (LPS) upregulates the expression of heme oxygenase-1 in fetal liver: the role of reactive oxygen species
Toxicol. Lett.
176
169-177
2008
Mus musculus (P14901), Mus musculus
Hsieh, C.H.; Jeng, S.F.; Hsieh, M.W.; Chen, Y.C.; Rau, C.S.; Lu, T.H.; Chen, S.S.
Statin-induced heme oxygenase-1 increases NF-kappaB activation and oxygen radical production in cultured neuronal cells exposed to lipopolysaccharide
Toxicol. Sci.
102
150-159
2008
Rattus norvegicus (P06762), Mus musculus (P14901)
Nakao, A.; Kaczorowski, D.J.; Sugimoto, R.; Billiar, T.R.; McCurry, K.R.
Application of heme oxygenase-1, carbon monoxide and biliverdin for the prevention of intestinal ischemia/reperfusion injury
J. Clin. Biochem. Nutr.
42
78-88
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Hu, C.M.; Liu, Y.H.; Cheah, K.P.; Li, J.S.; Lam, C.S.; Yu, W.Y.; Choy, C.S.
Heme oxygenase-1 mediates the inhibitory actions of brazilin in RAW264.7 macrophages stimulated with lipopolysaccharide
J. Ethnopharmacol.
121
79-85
2009
Mus musculus
Chen-Roetling, J.; Li, Z.; Chen, M.; Awe, O.O.; Regan, R.F.
Heme oxygenase activity and hemoglobin neurotoxicity are attenuated by inhibitors of the MEK/ERK pathway
Neuropharmacology
56
922-928
2009
Mus musculus
Piantadosi, C.A.; Withers, C.M.; Bartz, R.R.; Macgarvey, N.C.; Fu, P.; Sweeney, T.E.; Welty-Wolf, K.E.; Suliman, H.B.
Heme oxygenase-1 couples activation of mitochondrial biogenesis to anti-inflammatory cytokine expression
J. Biol. Chem.
286
16374-16385
2011
Mus musculus, Mus musculus C57/BL6
Fei, D.; Meng, X.; Kang, K.; Nan, C.; Zhao, M.; Pan, S.; Gao, M.; Yang, S.; Zhao, M.
Heme oxygenase-1 modulates thrombomodulin and activated protein C levels to attenuate lung injury in cecal ligation and puncture-induced acute lung injury mice
Exp. Lung Res.
38
173-182
2012
Mus musculus
Dorresteijn, M.J.; Paine, A.; Zilian, E.; Fenten, M.G.; Frenzel, E.; Janciauskiene, S.; Figueiredo, C.; Eiz-Vesper, B.; Blasczyk, R.; Dekker, D.; Pennings, B.; Scharstuhl, A.; Smits, P.; Larmann, J.; Theilmeier, G.; van der Hoeven, J.G.; Wagener, F.A.; Pickkers, P.; Immenschuh, S.
Cell-type-specific downregulation of heme oxygenase-1 by lipopolysaccharide via Bach1 in primary human mononuclear cells
Free Radic. Biol. Med.
78
224-232
2015
Homo sapiens, Mus musculus
Biswas, C.; Shah, N.; Muthu, M.; La, P.; Fernando, A.P.; Sengupta, S.; Yang, G.; Dennery, P.A.
Nuclear heme oxygenase-1 (HO-1) modulates subcellular distribution and activation of Nrf2, impacting metabolic and anti-oxidant defenses
J. Biol. Chem.
289
26882-26894
2014
Mus musculus
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