Disease relevance of Hmox1

• Rapid induction of heme oxygenase 1 mRNA and protein by hyperthermia in rat brain: heme oxygenase 2 is not a heat shock protein [1].
• Vascular heme oxygenase (HO) regulates vascular tone in normal conditions and in some pathologic circumstances (e.g., sepsis) [2].
• The blockade of protein translation before hemorrhage by cycloheximide reduced upregulation of HO-1/hsp32 mRNA significantly (65.4% reduction, P < .05), whereas the inducibility of hsp70 transcript was maintained [3].
• Increased vascular heme oxygenase-1 expression contributes to arterial vasodilation in experimental cirrhosis in rats [2].
• HO-1 was inducible in sinusoidal lining cells (hemorrhagic hypotension, LPS challenge), in periportal (cobalt chloride), or pericentral (GSH depletion, hemorrhagic hypotension) hepatocytes [3].

Psychiatry related information on Hmox1

• We suggest that increases in HO-1 transcript and protein reflect a means to elevate levels of antioxidants in cells with compromised defense mechanisms caused by stress [4].
• HBP23 was constitutively expressed in KC and up-regulated on the protein and messenger RNA (mRNA) level by LPS with a time response distinct from that of TNFalpha, but in coordination with that of heme oxygenase-1 (HO-1), which is the inducible isoform of the rate-limiting enzyme of heme degradation [5].
• Notably, the HO reaction proceeds without product inhibition by CO, which is generated in the conversion reaction of alpha-hydroxyheme to verdoheme, although CO is known to be a potent inhibitor of HO and other heme proteins [6].
• Icv injection of the NOS inhibitor Nomega-nitro-L-arginine-methylester (L-NAME; 50 microg) or the HO inhibitor tin protoporphyrin (SnPP; 20-25 microg) significantly blunted the plasma ACTH response to a 45-min session of intermittent electroshocks [7].
• Intrahippocampal, but not intra-amygdala, infusion of an inhibitor of heme oxygenase causes retrograde amnesia in the rat [8].

High impact information on Hmox1

• Heme oxygenase ((HO); EC 1.14.99.3) is the rate-limiting enzyme in the catabolism of heme to biliverdin (which is converted to bilirubin by biliverdin reductase), free iron and carbon monoxide (CO) [9].
• These findings, together with the neuronal localizations of heme oxygenase, suggest that carbon monoxide may function as a neurotransmitter [10].
• In primary cultures of olfactory neurons, zinc protoporphyrin-9, a potent selective inhibitor of heme oxygenase, depletes endogenous guanosine 3',5'-monophosphate (cGMP) [10].
• This novel action of the metal results from a potent induction effect on heme oxygenase, the enzyme that catalyzes heme oxidation in microsomes [11].
• Suppression of hyperbilirubinemia in the rat neonate by chromium-protoporphyrin. Interactions of metalloporphyrins with microsomal heme oxygenase of human spleen [12].

Chemical compound and disease context of Hmox1

• In contrast to HO-2, a significant increase in HO-1 on the whole organ level was noted by hemorrhagic hypotension, GSH depletion, and cobalt chloride injection [3].
• The heme released following subarachnoid hemorrhage is metabolized by heme-oxygenase (HO) to biliverdin and carbon monoxide (CO) with the release of iron [13].
• Administration of alpha-tocopherol (35 mmol/kg body weight) 2 h before paraquat treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels as well as heme oxygenase-1 and delta-aminolevulinic acid synthase induction [14].
• Administration of glutamine (300 mg/kg body weight) by gavage 24 h before CoCl2 treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels, and partially reverted heme oxygenase-1 induction [15].
• Heme oxygenase activity and some indices of antioxidant protection in rat liver and kidney in glycerol model of rhabdomyolysis [16].

Biological context of Hmox1

• However, the distinct stress models led to a strikingly different cell-type specific and sublobular expression pattern of HO-1 gene expression [3].
• The acute administration of an inhibitor of HO to cirrhotic rats, at a dose that normalized aortic HO activity, was associated with significantly greater effects on arterial pressure, total peripheral vascular resistance, and cardiac index, compared with effects in sham rats [2].
• In contrast, the other HO-1 products failed to block apoptosis or GADD153 expression during ER stress [17].
• The capacity of ER stress to stimulate the HO-1/CO system provides a novel mechanism by which this organelle regulates cell survival [17].
• Luciferase reporter assays indicated that ER stress stimulated HO-1 promoter activity via the antioxidant response element [17].

Anatomical context of Hmox1

• Six hours after heat shock, an intense increase in HO-1-like protein was observed in both Purkinje cells of the cerebellum and epithelial cells lining the cerebral aqueduct of the brain [1].
• HO-1 was mainly located in vascular smooth muscle cells of the arterial wall [2].
• Although both non-parenchymal cell fractions expressed HO-1 transcripts, HO-1 immunoreactive protein was restricted to Kupffer cells in the normal liver [3].
• To address this question, the expression and activity of HO in arterial vessels was studied in rats at 1, 2, and 4 weeks after bile duct ligation (BDL) or sham operation [2].
• A progressively increased expression of HO-1 was found in aorta and mesenteric arteries of BDL rats in a close chronologic relationship with the progression from acute cholestatic liver injury (1 week) to the fully developed cirrhosis with intense systemic arterial vasodilation (4 weeks) [2].

Associations of Hmox1 with chemical compounds

• Heme oxygenase (HO) catalyzes the oxidative cleavage of the alpha-mesocarbon of Fe-protoporphyrin-IX yielding equimolar amounts of biliverdin-IXa, iron, and carbon monoxide [3].
• Heme oxygenase-1 (HO-1) is a cytoprotective protein that catalyzes the degradation of heme to biliverdin, iron, and carbon monoxide (CO) [17].
• The induction of HO-1 by ER stress was blocked by actinomycin D or cycloheximide and was independent of any changes in HO-1 mRNA stability [17].
• Antioxidant treatment with either vitamin E or probucol almost completely normalized HO-1 overexpression in diabetic glomeruli, supporting the existence of oxidative stress in the glomeruli of early diabetes [18].
• This study investigated the time course of HO-1 and inducible nitric oxide synthase (iNOS) expression in the aortas of ovariectomized rats, and the regulatory relationship between the NO/NOS and the carbon monoxide/HO systems [19].
• Next we addressed the question whether induction of HO-1 or its byproduct carbon monoxide (CO) in organ donors targets these candidate markers related to enhanced immunogenicity [20].
• Insulin-induced HO-1 mRNA expression through activation of PI3-kinase/Akt pathway without affecting ERK and p38 MAPK [21].

Physical interactions of Hmox1

• Moreover, ER stress induced the nuclear import of Nrf2 and the binding of Nrf2 to the HO-1 antioxidant response element [17].

Regulatory relationships of Hmox1

• These results suggest that ADM induces HO-1 gene expression and cGMP formation in rat VSMCs [22].
• We conclude that HO isoform expression is segmented within the kidney and along the nephron and that treatment with an HO-1 inducer suppressed the levels of CYP4A and COX-2 proteins in a tissue-specific manner with concomitant effects on their activity [23].
• The iNOS inhibitor aminoguanidine significantly suppressed the induction of HO-1 [19].
• HO-1 was undetectable in CsA-treated rats compared to control while there was no change in HO-2 [24].
• Furthermore, TGF-beta1 downregulated HO-1 mRNA after its induction by IL-1beta in vascular smooth muscle cells in culture [25].

Other interactions of Hmox1

• Most (84%) of the CA1 pyramidal neurons examined expressed HO-1, COX-2, or both, and such expression showed good co-localization with c-Jun phosphorylation [26].
• Two of these proteins, heme oxygenase-1 and catalase, were expressed at relatively low levels until approximately the time of birth [27].
• Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes [28].
• In rings from normoxic rats, the HO inhibitor tin protoporphyrin IX (SnPP IX, 10 microM) did not alter the response to phenylephrine or ET-1 [29].
• Paraquat-generated oxidative stress in rat liver induces heme oxygenase-1 and aminolevulinic acid synthase [14].

Analytical, diagnostic and therapeutic context of Hmox1

• The induction of a 1.8-kilobase HO-1 mRNA resulted in a pronounced increase in HO-1 protein 6 h after hyperthermia, as detected by both Western immunoblot and RIA [1].
• Immunocytochemistry of rat brain showed discrete localization of HO-1-like protein only in neurons of select brain regions [1].
• Because FGF-1 potently activates astroglia and exerts a direct neuroprotection after spinal cord injury or axotomy, we examined whether it regulated the expression of inducible and cytoprotective heme oxygenase-1 (HO-1) enzyme in astrocytes [30].
• Two days following five cycles of 10 min ischemia and 10 min reperfusion, heme oxygenase (HO) and calcium-dependent nitric oxide synthase (cNOS) activities were increased 2- and 2.5-fold (p <.05), respectively [31].
• Removal of NOS activity completely removed the benefit afforded microvascular perfusion, while inhibition of HO activity prevented the parenchymal protection [31].

References