Disease relevance of HMOX1

• Nucleotide sequence of cDNA for porcine heme oxygenase and its expression in Escherichia coli [1].
• Heme oxygenase (HO), the heme-degrading enzyme, has shown anti-inflammatory effects in several models of pulmonary diseases [2].
• In newborn pigs, the mechanism of seizure-induced cerebral hyperemia involves carbon monoxide (CO), the vasodilator product of heme catabolism by heme oxygenase (HO) [3].
• Our results suggest a protective role of HO activation during hyperdynamic porcine endotoxemia possibly as a result of an interaction with the LPS-induced increase in NO formation [4].
• The effects of the HO inhibitor, tin protoporphyrin (SnPP), on brain electrical activity and pial arteriolar diameter were examined using quantitative electroencephalography (EEG) and cranial window techniques in the bicuculline model of sustained generalized seizures in newborn pigs [5].

High impact information on HMOX1

• Purification and properties of heme oxygenase from pig spleen microsomes [6].
• Ionotropic glutamate receptors in cerebral microvascular endothelium are functionally linked to heme oxygenase [7].
• Glutamate, aspartate, ACPD, AMPA, (RS)-2-amino-(3-hydroxy-5- -butylisoxazol-4-yl)propanoic acid (ATPA), and kainate (10(-5) mol/L) increased HO-directed CO formation by isolated cerebral microvessels and by cultured CMVEC [7].
• A cytoprotective effect comparable to ANP was observed when preincubating the cells with 8-bromo cGMP (1-100 microM) or the antioxidant heme oxygenase (HO) metabolite bilirubin (0.1-10 microM) [8].
• Moreover, incubation with ANP or 8-bromo cGMP led to increased HO activity, i.e., formation of bilirubin in the cell lysate (up to 3-fold over basal) [8].

Chemical compound and disease context of HMOX1

• Acute maternal oral administration of 4 g ethanol/kg maternal body weight at GD 62 did not affect HO activity in these three fetal brain areas compared with control fetuses (maternal administration of isocaloric sucrose or water) [9].

Biological context of HMOX1

• The nucleotide sequence of a cDNA for porcine heme oxygenase was determined [1].
• A prokaryotic expression plasmid carrying porcine heme oxygenase cDNA was constructed and transfected into Escherichia coli cells [1].
• Tin protoporphyrin-IX (SnPP; 19 microM), an inhibitor of HO activity, completely abolished ANP-induced cytoprotection [8].
• HO upregulation by repeated administrations of hemin (50 mg/kg i.p.) significantly decreased airway responsiveness in control animals and airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals [2].
• Systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of the HO-inhibitor tin-mesoporphyrin (SnMP) were assessed in anesthetized and mechanically ventilated animals [4].

Anatomical context of HMOX1

• The full-length heme oxygenase expressed was localized in the bacterial membranes [1].
• Delta 12-Prostaglandin (PG) J2 caused porcine aortic endothelial cells to synthesize a 31,000-dalton heme oxygenase and a 67,000-dalton protein (p67) [10].
• Zinc protoporphyrin-IX (ZnPPn), an inhibitor of heme oxygenase, effectively inhibited VIP-induced relaxations of tracheal smooth muscle [11].
• These findings suggest that HO in the cerebral microcirculation is rapidly activated during seizures and provides endogenous protection against seizure-induced vascular injury [3].
• SnPP (3 mg/kg iv) blocked dilation to heme and reduced the CO level in cortical periarachnoid cerebrospinal fluid, indicating HO inhibition in the cerebral microcirculation [3].

Associations of HMOX1 with chemical compounds

• Vasodilator effects of glutamate in the cerebral circulation are, in part, mediated by carbon monoxide (CO), which is formed from heme via the heme oxygenase (HO) pathway [7].
• There was a reciprocal relationship between the level of intracellular GSH, and that of the induction of heme oxygenase and p67 syntheses by delta 12-PGJ2 [10].
• Inability of the NADH-cytochrome b5 reductase system to initiate heme degradation yielding biliverdin IX alpha from the oxygenated form of heme . heme oxygenase complex [12].
• Heme oxygenase activity, drug metabolism, amd ascorbic acid distribution in the livers of ascorbic acid-deficient guinea pigs [13].
• Moreover, the induction of heme oxygenase and p67 syntheses by the thiol-reactive agents arsenite and diethylmaleate was also inhibited by GSH treatment and enhanced by BSO treatment [10].

Other interactions of HMOX1

• This observation dissociates the response to low oxygenation of alphaB-crystallin and other stress-associated proteins including Hsp27, and it indicates that heme oxygenase is not alone among HSPs in its oxygen-related gene expression [14].
• Stereologic description of the changing expression of constitutive nitric oxide synthase and heme oxygenase in the enteric plexuses of the pig small intestine during development [15].
• Activation of the inducible NO synthase by the synergistic action of bacterial lipopolysaccharide (250 ng/ml) and interferon-gamma (100 U/ml) also increased endothelial heme oxygenase activity by 3.2-fold (P < 0.05 vs control) [16].

Analytical, diagnostic and therapeutic context of HMOX1

• Therefore we studied the role of HO during long-term porcine hyperdynamic endotoxemia characterized by a sustained increase in cardiac output resulting from colloid resuscitation to maintain mean arterial pressure > 60 mmHg [4].
• The purified heme oxygenase showed an apparent molecular weight of 157,000 +/- 7,000 daltons when estimated by gel filtration [17].
• In this study, we have analyzed the occurrence of PACAP 38 and the corresponding occurrence of heme oxygenase (HO), the rate-limiting enzyme for CO production, in guinea pig trachea, using immunocytochemistry [18].

References