Disease relevance of Hmox2

• In contrast, the two HO-2 homologous transcripts (1.3 and 1.9 kilobases) did not respond to heat shock; neither the ratio nor the level of the two messages differed from that of the control when measured either at 1, 6, or 24 h after hyperthermia [1].
• 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 [2].
• Presently a rat HO-2 cDNA (Rotenberg, M.O., and Maines, M. D. (1990) J. Biol. Chem. 265, 7501-7506) was used to generate a construct with a neutral hydrophobicity profile at its COOH terminus for expression of nearly full-length HO-2 protein in Escherichia coli [3].
• Interaction between endothelial heme oxygenase-2 and endothelin-1 in altered aortic reactivity after hypoxia in rats [4].
• We show expression of HO-1 and HO-2 at both the transcription and protein levels under normal conditions in the heart and descending aorta, and demonstrate the sensitivity of only the HO-1 isozyme to heat stress in these tissues [5].

Psychiatry related information on Hmox2

• The heme oxygenase system and cellular defense mechanisms. Do HO-1 and HO-2 have different functions [6]?
• In light of the recently reported inhibitory interaction between HO-2/CO and amyloid-beta, a marker of Alzheimer's disease (AD), we speculate that HO-2/CO signaling may be a defective component of cholinergic neurotransmission in the pathophysiology of AD, whose manifestations include disintegration of circadian timing [7].

High impact information on Hmox2

• Rat renal interlobar arteries express heme oxygenase 2 (HO-2) and manufacture carbon monoxide (CO), which is released into the headspace gas [8].
• Assessment of phenylephrine-induced tension development revealed reduction of the EC(50) in vessels treated with HO-2 AS-ODN, CrMP, or TEA [8].
• Reverse transcriptase-PCR (RT-PCR) and Western blot analyses indicate expression of the constitutive HO form, HO-2, in the rat cortex and outer medulla [9].
• In contrast, HO-2 protein expression was not changed in hypertensive rat aortas [10].
• Using immunocytochemistry, we demonstrate that heme oxygenase 2 is localized to glomus cells in the cat and rat carotid bodies [11].

Chemical compound and disease context of Hmox2

• The visible and pyridine hemochromogen spectra suggest that the Escherichia coli expressed purified HO-2 is a hemoprotein [12].
• In this model of focal ischemia, perilesional, constitutively nitric oxide synthase-I containing neurons survived and co-expressed antioxidative enzymes, such as manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and cytosolic glutathione peroxidase [13].
• Depletion of endogenous serotonin synthesis with p-CPA attenuates upregulation of constitutive isoform of heme oxygenase-2 expression, edema formation and cell injury following a focal trauma to the rat spinal cord [14].
• Role of carbon monoxide (CO) in hyperthermic brain injury induced brain pathology was examined in a rat model using immunohistochemistry of the hemeoxygenase-2 (HO-2) enzyme [15].

Biological context of Hmox2

• Approximately 43% amino acid homology was detected between the HO-2 insert and the published amino acid sequence of heme oxygenase [16].
• These observations demonstrate tissue and cell specificity of HO-2 gene expression and suggest that in the testis, HO-2 expression is regulated at the transcriptional and translational levels [17].
• Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene [18].
• Neither gene had any introns and consisted only of exon 2 through 5 of the HO-2 gene, though their sequences were not completely identical with that of HO-2 [18].
• The localization of heme oxygenase-2 in the retina implies that its function is not associated with phototransduction [19].

Anatomical context of Hmox2

• HO-2 messenger RNA (mRNA) and protein were constitutively expressed in hepatocytes, Kupffer/endothelial-, and stellate (Ito-) cell enriched fractions [2].
• Using antibody to HO-2, four testis clones and two liver clones were isolated, and one liver and one testis clone were sequenced [16].
• HO-2 is expressed by aortic endothelial cells early during hypoxic exposure and impairs ET-1-mediated potentiation of contraction to alpha-adrenoceptor stimulation [4].
• Removal of endothelium abolished the increase in HO-2 immunoreactivity [4].
• Interestingly, although abundant HO-2 mRNA can be detected by in situ hybridization in spermatogonia, spermatocytes, and spermatids, HO-2 protein was detected, by immunocytochemistry, only in spermatids [17].

Associations of Hmox2 with chemical compounds

• A multistep protocol developed for isolation of HO-2 resulted in a homogeneous protein with a specific activity up to 6,500 nmol of bilirubin/mg/h. Based on SDS-polyacrylamide gel electrophoresis and Western blot analyses, the protein had an apparent molecular mass of approximately 34 kDa [3].
• Major differences, however, were noted in the amino acid composition of the two forms including the presence of 3 cysteine/cystine residues in HO-2 only [16].
• The neurotoxic heme is usually detoxified by the constitutive heme oxygenase-2 (HO-2) and its inducible isoform HO-1(heat shock protein 32) resulting in the formation of biliverdin which becomes reduced to bilirubin, carbon monoxide (CO), and iron [20].
• In adult rat testis, corticosterone treatment, however, was not an effective regulator of HO-2 transcript populations or levels [21].
• HO-2 is a constitutive isoform of heme oxygenase (HO), a microsomal enzyme that catalyzes the cleavage of the heme ring to form ferrous iron, carbon monoxide, and biliverdin [22].

Regulatory relationships of Hmox2

• The transcripts for HO-1 in the renal outer medulla and inner medulla were 2.5 and 3.7 times that expressed in the renal cortex and those for HO-2 in the outer medulla and inner medulla were 1.3 and 1.6 times that expressed in the renal cortex, respectively [23].

Other interactions of Hmox2

• Rapid induction of heme oxygenase 1 mRNA and protein by hyperthermia in rat brain: heme oxygenase 2 is not a heat shock protein [1].
• Interaction of Fe-protoporphyrin IX and heme analogues with purified recombinant heme oxygenase-2, the constitutive isozyme of the brain and testes [3].
• Expression of the constitutive enzymes HO-2 and endothelial NOS did not differ significantly between sham-operated and Ovx rats [24].
• In the corpus cavernosum of SHR, expression of the HO-2 and nNOS genes was similar, and NOx levels after EFS were similar to those of WKY. cGMP levels after EFS and the relaxation evoked by the NO donor was lower in SHR than WKY [25].
• TGF-beta1 also decreased HO-1 but not HO-2 protein expression in these cells [26].

Analytical, diagnostic and therapeutic context of Hmox2

• HO-2 immunohistochemistry showed that the number of HO-2-positive neurons in most perilesional regions remained constant [20].
• Northern blot analysis was used to demonstrate the presence of five transcripts for HO-2 in rat testis mRNA; they range from approximately 1.3 to approximately 2.1 kg in length with a predominant 1.45-kb message; three of the transcripts, approximately 1.45 kb, approximately 1.7 kb, and approximately 2.1 kg, are unique to testis [17].
• Frozen tissues were subjected to HO-1 and HO-2 mRNA expression by real-time RT-PCR and HO activity determination [27].
• The ratio of the two HO-2 homologous transcripts (approximately 1.9 and 1.3 Kb) present in the atrium, ventricles and descending aorta and their levels were not altered by hyperthermia (42 degrees C, 20 min) when measured 1 or 6 hr after treatment [5].
• Antiserum to the liver HO-1 did not recognize the testicular HO-2 when examined by double immunodiffusion or by Western immunoblotting [28].

References