Genomes and Genes
Gene Symbol: Hmox2
Description: heme oxygenase 2
Alias: HO-2, HO2, heme oxygenase 2, heme oxygenase (decycling) 2
- Zhuang H, Littleton Kearney M, DORE S. Characterization of heme oxygenase in adult rodent platelets. Curr Neurovasc Res. 2005;2:163-8 pubmed..Further investigation into the functional properties of HO itself, heme degradation, and heme bioactive metabolites remains to be conducted to determine the role of HO on platelet dynamics and on microvasculature. ..
- Yet S, Perrella M, Layne M, Hsieh C, Maemura K, Kobzik L, et al. Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 null mice. J Clin Invest. 1999;103:R23-9 pubmed..Our data suggest that in the absence of HO-1, cardiomyocytes have a maladaptive response to hypoxia and subsequent pulmonary hypertension. J.Clin. Invest. 103:R23-R29 (1999). ..
- Li X, Clark J. Spinal cord nitric oxide synthase and heme oxygenase limit morphine induced analgesia. Brain Res Mol Brain Res. 2001;95:96-102 pubmed..In spinal cord slices from either nNOS or HO-2 null-mutant animals morphine did not stimulate cGMP production. Taken together our data suggest that spinal monoxide generation modifies the acute analgesic actions of morphine. ..
- Chang E, Wong R, Vreman H, Igarashi T, Galo E, Sharp F, et al. Heme oxygenase-2 protects against lipid peroxidation-mediated cell loss and impaired motor recovery after traumatic brain injury. J Neurosci. 2003;23:3689-96 pubmed..These findings demonstrate that HO-2 expression protects neurons against TBI by reducing lipid peroxidation via the catabolism of free heme. ..
- Li B, Takeda K, Ishikawa K, Yoshizawa M, Sato M, Shibahara S, et al. Coordinated expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 and heme oxygenase 2: evidence for a regulatory link between glycolysis and heme catabolism. Tohoku J Exp Med. 2012;228:27-41 pubmed..We therefore postulate that PFKFB4 and HO-2 are expressed in a coordinated manner to maintain glucose homeostasis. ..
- Lundvig D, Scharstuhl A, Cremers N, Pennings S, Te Paske J, van Rheden R, et al. Delayed cutaneous wound closure in HO-2 deficient mice despite normal HO-1 expression. J Cell Mol Med. 2014;18:2488-98 pubmed publisher..However, whether aberrant CXCL-11 expression in HO-2 KO mice is caused by or is causing delayed wound healing needs to be further investigated. ..
- Watanabe S, Akagi R, Mori M, Tsuchiya T, Sassa S. Marked developmental changes in heme oxygenase-1 (HO-1) expression in the mouse placenta: correlation between HO-1 expression and placental development. Placenta. 2004;25:387-95 pubmed..The correlation between HO-1 expression and placental development suggests that HO-1 might be essential for normal embryonic development. ..
- Rattan S, Regan R, Patel C, de Godoy M. Nitric oxide not carbon monoxide mediates nonadrenergic noncholinergic relaxation in the murine internal anal sphincter. Gastroenterology. 2005;129:1954-66 pubmed..i-NANC relaxations of mouse IAS are primarily mediated via NO (by nNOS activity) and partly via VIP. CO directly relaxes the mouse IAS but does not play any significant role in the i-NANC relaxation. ..
- Ma B, Day J, Phillips H, Slootsky B, Tolosano E, DorÃ© S. Deletion of the hemopexin or heme oxygenase-2 gene aggravates brain injury following stroma-free hemoglobin-induced intracerebral hemorrhage. J Neuroinflammation. 2016;13:26 pubmed publisher..Hemopexin (Hpx) has the highest binding affinity to heme and participates in its transport, while heme oxygenase 2 (HO2) is the rate-limiting enzyme for the degradation of heme...
- Stout J, Gousset M, Drummond H, Gray W, Pruett B, Stec D. Sex-specific effects of heme oxygenase-2 deficiency on renovascular hypertension. J Am Soc Hypertens. 2013;7:328-35 pubmed publisher..These results demonstrate a sex-specific effect of HO-2 deficiency on the development of renovascular hypertension and its effects on the heart in response to the increase in blood pressure. ..
- Vanella L, Li Volti G, Guccione S, Rappazzo G, Salvo E, Pappalardo M, et al. Heme oxygenase-2/adiponectin protein-protein interaction in metabolic syndrome. Biochem Biophys Res Commun. 2013;432:606-11 pubmed publisher..Thus, crosstalk between HO-2 and HO-1 could be manipulated in a therapeutic approach to ameliorate the deleterious effects of obesity and the metabolic syndrome. ..
- Ortega Saenz P, Pascual A, Gómez Díaz R, Lopez Barneo J. Acute oxygen sensing in heme oxygenase-2 null mice. J Gen Physiol. 2006;128:405-11 pubmed..Therefore, HO-2 is not a universally used acute O(2) sensor. ..
- Parfenova H, Basuroy S, Bhattacharya S, Tcheranova D, Qu Y, Regan R, et al. Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection. Am J Physiol Cell Physiol. 2006;290:C1399-410 pubmed..Although HO-1, when induced, provides powerful protection, HO-2 is an essential endogenous anti-apoptotic factor against glutamate toxicity in the cerebral vascular endothelium. ..
- Han F, Takeda K, Yokoyama S, Ueda H, Shinozawa Y, Furuyama K, et al. Dynamic changes in expression of heme oxygenases in mouse heart and liver during hypoxia. Biochem Biophys Res Commun. 2005;338:653-9 pubmed..3-fold, respectively, in the heart at 28 days of hypoxia. Thus, hypoxia induces or represses the expression of HO-1 and HO-2 in vivo, depending on cellular microenvironments. ..
- Goto S, Sampei K, Alkayed N, DORE S, Koehler R. Characterization of a new double-filament model of focal cerebral ischemia in heme oxygenase-2-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2003;285:R222-30 pubmed..In wild-type (WT) and heme oxygenase-2 gene-deleted (HO2-/-) mice, infarcts were not reproducibly achieved with the standard intraluminal filament technique...
- Kang L, Grande J, Farrugia G, Croatt A, Katusic Z, Nath K. Functioning of an arteriovenous fistula requires heme oxygenase-2. Am J Physiol Renal Physiol. 2013;305:F545-52 pubmed publisher..HO-2 deficiency also led to lower AVF blood flow when AVFs were created in uremia, the latter induced by subtotal nephrectomy. We conclude that HO-2 critically contributes to the adequacy of AVF blood flow and function. ..
- Han F, Takeda K, Ishikawa K, Ono M, Date F, Yokoyama S, et al. Induction of lipocalin-type prostaglandin D synthase in mouse heart under hypoxemia. Biochem Biophys Res Commun. 2009;385:449-53 pubmed publisher..L-PGDS expression is induced in the myocardium under hypoxemia, which may reflect the adaptation to the hemodynamic stress. ..
- Zakhary R, Poss K, Jaffrey S, Ferris C, Tonegawa S, Snyder S. Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide. Proc Natl Acad Sci U S A. 1997;94:14848-53 pubmed..In nNOSDelta/Delta animals, NOS inhibitors selectively lost their efficacy, and HO inhibitors were inactive in HO-2(Delta)/Delta animals. ..
- Liang D, Li X, Lighthall G, Clark J. Heme oxygenase type 2 modulates behavioral and molecular changes during chronic exposure to morphine. Neuroscience. 2003;121:999-1005 pubmed..Furthermore, these studies suggest that the mechanisms underlying analgesic tolerance and opioid-induced hypersensitivity are at least somewhat distinct. ..
- Basuroy S, Bhattacharya S, Tcheranova D, Qu Y, Regan R, Leffler C, et al. HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-alpha in cerebral vascular endothelial cells. Am J Physiol Cell Physiol. 2006;291:C897-908 pubmed..We conclude that HO-2 is critical for protection of cerebrovascular endothelium against apoptotic changes induced by oxidative stress and cytokine-mediated inflammation. ..
- Regan R, Chen J, Benvenisti Zarom L. Heme oxygenase-2 gene deletion attenuates oxidative stress in neurons exposed to extracellular hemin. BMC Neurosci. 2004;5:34 pubmed..These results suggest that HO-2 gene deletion protects neurons in mixed neuron-astrocyte cultures from heme-mediated oxidative injury. Selective inhibition of neuronal HO-2 may have a beneficial effect after CNS hemorrhage. ..
- Roth M, Rupp M, Hofmann S, Mittal M, Fuchs B, Sommer N, et al. Heme oxygenase-2 and large-conductance Ca2+-activated K+ channels: lung vascular effects of hypoxia. Am J Respir Crit Care Med. 2009;180:353-64 pubmed publisher..It is demonstrated that neither deletion of HO-2 nor BK channels affect acute, sustained, and chronic vascular responses to alveolar hypoxia in the lung. ..
- Tracy K, Dibling B, Spike B, Knabb J, Schumacker P, Macleod K. BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy. Mol Cell Biol. 2007;27:6229-42 pubmed..These studies identify BNIP3 as a key regulator of hypoxia-induced autophagy and suggest a novel role for the RB tumor suppressor in preventing nonapoptotic cell death by limiting the extent of BNIP3 induction in cells. ..
- Burnett A, Johns D, Kriegsfeld L, Klein S, Calvin D, Demas G, et al. Ejaculatory abnormalities in mice with targeted disruption of the gene for heme oxygenase-2. Nat Med. 1998;4:84-7 pubmed..In the nervous system CO is formed by a subtype of heme oxygenase (HO) designated HO2. HO2 is localized to discrete neuronal populations in the brain resembling localizations of soluble guanylyl ..
- Watkins C, Boehning D, Kaplin A, Rao M, Ferris C, Snyder S. Carbon monoxide mediates vasoactive intestinal polypeptide-associated nonadrenergic/noncholinergic neurotransmission. Proc Natl Acad Sci U S A. 2004;101:2631-5 pubmedCarbon monoxide (CO) synthesized by heme oxygenase 2 (HO2) and nitric oxide (NO) produced by neuronal NO synthase (nNOS) mediate nonadrenergic/noncholinergic (NANC) intestinal relaxation...
- Kim Y, Zhuang H, Koehler R, DORE S. Distinct protective mechanisms of HO-1 and HO-2 against hydroperoxide-induced cytotoxicity. Free Radic Biol Med. 2005;38:85-92 pubmed..The differences in subcellular localization of HO-1 and HO-2 could explain some of the discrepancies in their cellular activity and enzymatic protective mechanisms. ..
- Kang L, Hillestad M, Grande J, Croatt A, Barry M, Farrugia G, et al. Induction and functional significance of the heme oxygenase system in pathological shear stress in vivo. Am J Physiol Heart Circ Physiol. 2015;308:H1402-13 pubmed publisher..Induction of HO-1 may reside in NF-ÎºB activation, and, along with induced HO-2, such upregulation of HO-1 provides a countervailing vasoprotective response in pathological shear stress in vivo. ..
- Saito Ohara F, Ikeuchi T, Matsumoto M, Kurata S. Assignment of the mouse heme oxygenase genes: heme oxygenase-1 (Hmox1) to chromosome 10 band C1 and heme oxygenase-2 (Hmox2) to chromosome 16 band B1. Cytogenet Cell Genet. 1997;77:180-1 pubmed
- Sedlak T, Saleh M, Higginson D, Paul B, Juluri K, Snyder S. Bilirubin and glutathione have complementary antioxidant and cytoprotective roles. Proc Natl Acad Sci U S A. 2009;106:5171-6 pubmed publisher..RNA interference depletion of BVR increases oxidation of lipids more than protein. Depletion of BVR or GSH augments cell death in an oxidant-specific fashion. ..
- Wang J, Dore S. Heme oxygenase 2 deficiency increases brain swelling and inflammation after intracerebral hemorrhage. Neuroscience. 2008;155:1133-41 pubmed publisher..We have previously reported a neuroprotective role for HO2 in early brain injury after ICH; however, in vivo data that specifically address the role of HO2 in brain edema and ..
- Chen R, Yuan H, Zhang T, Wang Z, Hu A, Wu L, et al. Heme oxygenase-2 suppress TNF-? and IL6 expression via TLR4/MyD88-dependent signaling pathway in mouse cerebral vascular endothelial cells. Mol Neurobiol. 2014;50:971-8 pubmed publisher..CLI-095 and HO-2 overexpression potently suppressed TLR4/MyD88-dependent proinflammatory cytokine expression in CMVEC. These results suggest that HO-2 plays an important role in protecting CMVEC against cytokine-mediated inflammation. ..
- Qin X, Kwansa H, Bucci E, DORE S, Boehning D, Shugar D, et al. Role of heme oxygenase-2 in pial arteriolar response to acetylcholine in mice with and without transfusion of cell-free hemoglobin polymers. Am J Physiol Regul Integr Comp Physiol. 2008;295:R498-504 pubmed publisher..The role of constitutive HO2 in the pial arteriolar dilatory response to acetylcholine was determined by using 1) HO2-null mice (HO2-/-), 2) the ..
- Xue L, Farrugia G, Miller S, Ferris C, Snyder S, Szurszewski J. Carbon monoxide and nitric oxide as coneurotransmitters in the enteric nervous system: evidence from genomic deletion of biosynthetic enzymes. Proc Natl Acad Sci U S A. 2000;97:1851-5 pubmed..The colocalization of their respective biosynthetic enzymes, neuronal NO synthase (nNOS) and heme oxygenase-2 (HO2), in enteric neurons and altered intestinal function in mice with genomic deletion of the enzymes (nNOS(Delta/Delta)..
- Goodman A, Chander P, Rezzani R, Schwartzman M, Regan R, Rodella L, et al. Heme oxygenase-2 deficiency contributes to diabetes-mediated increase in superoxide anion and renal dysfunction. J Am Soc Nephrol. 2006;17:1073-81 pubmed..These observations indicate that HO activity is essential in preserving renal function and morphology in STZ-induced diabetic mice probably via mitigation of concomitant oxidative stress. ..
- Li X, Clark J. Heme oxygenase type 2 participates in the development of chronic inflammatory and neuropathic pain. J Pain. 2003;4:101-7 pubmed..Our results indicate that HO-2 participates in the thermal hyperalgesia and mechanical allodynia that occur in 2 commonly used models of chronic inflammatory and neuropathic pain. ..
- Han F, Takeda K, Ono M, Date F, Ishikawa K, Yokoyama S, et al. Hypoxemia induces expression of heme oxygenase-1 and heme oxygenase-2 proteins in the mouse myocardium. J Biochem. 2010;147:143-51 pubmed publisher..Unexpectedly, HO-1 protein level was lower by 35% in the HO-2(-/-) mouse liver than the wild-type liver. These results indicate that the expression of HO-1 protein is regulated in a tissue-specific manner under hypoxemia. ..
- Stec D, Vera T, Storm M, McLemore G, Ryan M. Blood pressure and renal blow flow responses in heme oxygenase-2 knockout mice. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1822-8 pubmed publisher..Our data indicate that blood pressure and RBF responses to increased ANG II or inhibition of nitric oxide are not significantly enhanced in HO-2 KO mice. ..
- Shah Z, Nada S, Dore S. Heme oxygenase 1, beneficial role in permanent ischemic stroke and in Gingko biloba (EGb 761) neuroprotection. Neuroscience. 2011;180:248-55 pubmed publisher..Targeting this pathway could lead to neuroprotective agents against ischemic stroke. ..
- Chen J, Tu Y, Moon C, Nagata E, Ronnett G. Heme oxygenase-1 and heme oxygenase-2 have distinct roles in the proliferation and survival of olfactory receptor neurons mediated by cGMP and bilirubin, respectively. J Neurochem. 2003;85:1247-61 pubmed..These results support a role for HO, the CO-cGMP signaling system and bilirubin in neurodevelopment and in response to injury. ..
- Namiranian K, Koehler R, Sapirstein A, DORE S. Stroke outcomes in mice lacking the genes for neuronal heme oxygenase-2 and nitric oxide synthase. Curr Neurovasc Res. 2005;2:23-7 pubmed..The results suggest that the deleterious action of nNOS would counteract the role of HO-2 in neuroprotection. ..
- Zhao H, Wong R, Nguyen X, Kalish F, Mizobuchi M, Vreman H, et al. Expression and regulation of heme oxygenase isozymes in the developing mouse cortex. Pediatr Res. 2006;60:518-23 pubmed..Therefore, we conclude that HO-1 gene expression in the cortex is developmentally-regulated and that methylation of the HO-1 CpG island is not associated with the down-regulation of the gene. ..
- Yoneyama Sarnecky T, Olivas A, Azari S, Ferriero D, Manvelyan H, Noble Haeusslein L. Heme oxygenase-2 modulates early pathogenesis after traumatic injury to the immature brain. Dev Neurosci. 2010;32:81-90 pubmed publisher..Together, these findings demonstrate that deficiency in HO-2 alters both the kinetics of secondary damage and fine motor recovery after TBI. ..
- Gibbs L, Willis D, Morgan M. The identification and expression of heme oxygenase-2 alternative transcripts in the mouse. Gene. 1998;221:171-7 pubmed..These alternative murine HO-2 transcripts suggest that mechanisms such as mRNA transport, translational efficiency or mRNA turnover may be implicated in the regulation of HO-2 gene expression, most notably in the testis. ..
- Li A, Xi Q, Umstot E, Bellner L, Schwartzman M, Jaggar J, et al. Astrocyte-derived CO is a diffusible messenger that mediates glutamate-induced cerebral arteriolar dilation by activating smooth muscle Cell KCa channels. Circ Res. 2008;102:234-41 pubmed..Our study explains the astrocyte and HO dependence of glutamatergic functional hyperemia observed in the newborn cerebrovascular circulation in vivo. ..
- Liang D, Li X, Clark J. Formalin-induced spinal cord calcium/calmodulin-dependent protein kinase II alpha expression is modulated by heme oxygenase in mice. Neurosci Lett. 2004;360:61-4 pubmed..These findings suggest that time-dependent CaMKIIalpha expression may underlie central sensitization and allodynia induced by hindpaw formalin injection, and that this process is modulated by HO-2. ..
- Biteman B, Hassan I, Walker E, Leedom A, Dunn M, Seta F, et al. Interdependence of lipoxin A4 and heme-oxygenase in counter-regulating inflammation during corneal wound healing. FASEB J. 2007;21:2257-66 pubmed..Collectively, results demonstrate a critical role for LXA4 in inflammatory/reparative responses and provide the first evidence that 12/15-LOX and HO systems function in concert to control inflammation. ..
- Zhang Y, Furuyama K, Adachi T, Ishikawa K, Matsumoto H, Masuda T, et al. Hypoxemia and attenuated hypoxic ventilatory responses in mice lacking heme oxygenase-2: evidence for a novel role of heme oxygenase-2 as an oxygen sensor. Adv Exp Med Biol. 2006;580:161-6; discussion 351-9 pubmed
- Matsumoto M, Saito Ohara F, Hoshi M, Kurata S. Cloning and sequencing of mouse complementary DNA for heme oxygenase-2. J Biochem. 1996;120:1079-81 pubmed..8 kDa. The nucleotide sequence is 85.6% identical and the amino acid sequence 87% identical to those of the human protein. The corresponding mRNA is present in brain and testis, but not in ovary, kidney, liver, or spleen. ..
- Morikawa T, Kajimura M, Nakamura T, Hishiki T, Nakanishi T, Yukutake Y, et al. Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway. Proc Natl Acad Sci U S A. 2012;109:1293-8 pubmed publisher..Thus, in intact adult brain cerebral cortex of HO-2-null mice, imaging mass spectrometry reveals an impaired ability to maintain ATP levels on hypoxia. ..
- Sha L, Farrugia G, Harmsen W, Szurszewski J. Membrane potential gradient is carbon monoxide-dependent in mouse and human small intestine. Am J Physiol Gastrointest Liver Physiol. 2007;293:G438-45 pubmed..record the RMPs of circular smooth muscle cells at different depths in the human small intestine and in wild-type, HO2-KO, and W/W(V) mutant mouse small intestine...
- Chen J, Tu Y, Connolly E, Ronnett G. Heme oxygenase-2 protects against glutathione depletion-induced neuronal apoptosis mediated by bilirubin and cyclic GMP. Curr Neurovasc Res. 2005;2:121-31 pubmed..Taken together, these results suggest that HO-2 plays a major role in neuroprotection from oxidative stress, an effect that is mediated by cGMP and bilirubin. ..
- Li X, Clark J. Heme oxygenase type 2 plays a role in formalin-induced nociception. Pain. 2000;86:75-80 pubmed..Taken together our evidence indicates that HO plays an important role in nociceptive signaling related to inflammatory-type pain, and that HO-2 is the isozyme mediating this nociception. ..
- Wang J, Zhuang H, DORE S. Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage. Neurobiol Dis. 2006;22:473-6 pubmedRecent studies suggest a neuroprotective function for heme oxygenase 2 (HO2) in acute brain injury and ischemia...