• 약학회지
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• 제45권1호
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• pp.78-84
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• 2001

Heme oxygenase is a rate-limiting enzyme in heme catabolism that cleaves heme to form biliverdin, iron, and carbon monoxide. Heme oxygenase-1 is expressed in many types of cells and tissues and is highly induced in response to oxidative stress. Carbon monoxide, one of the products of heme oxygenase, can stimulate soluble guanylate cyclase and dilate the vascular smooth muscle. So, the induction of heme oxygenase by lipopolysaccharide (LPS)-induced oxydative stress and the effect of the resultant carbon monoxide on aortic contractility were examined in this study. Zinc protoporphyrine IX (ZnPP), a inhibitor of heme oxygenase, elicited weak contraction of thoracic aortic ring, and this effect was more potent in aorta of LPS-treated rats than control and was blocked by methylene blue. The hyperreactivity to ZnPP in LPS-treated group was blocked by co-treatment with aminoguanidine. In the aortic ring of LPS-treated rats, ZnPP didn't change the vasoreactivity to phenylephrine or acetylcholine. ZnPP elicited hyper-tensive effect in concious rats, and pretreatment with LPS did not affect this effect. Prazosin significantly diminished the hypertensive effect of ZnPP. These results indicate that LPS induced heme oxygenase in aotra, and the resultant carbon monoxide diminished the aortic reactivity to vasoconstrictor.

• IMMUNE NETWORK
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• 제9권1호
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• pp.12-19
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• 2009

Heme oxygenase (HO)-1 is an inducible enzyme that catalyzes the first and rate-limiting step in the oxidative degradation of free heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV), the latter being subsequently converted into bilirubin (BR). HO-1, once expressed during inflammation, forms high concentrations of its enzymatic by-products that can influence various biological events, and this expression is proven to be associated with the resolution of inflammation. The degradation of heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of ferrous iron by ferritin all concertedly contribute to the anti-inflammatory effects of HO-1. This review focuses on the anti-inflammatory mechanisms of HO-1 actions and its roles in inflammatory diseases.

• Parasites, Hosts and Diseases
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• 제48권1호
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• pp.15-21
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• 2010

Astrocytes are the most abundant cells in the central nervous system that play roles in maintaining the blood-brain-barrier and in neural injury, including cerebral malaria, a severe complication of Plasmodium falciparum infection. Prostaglandin (PG) $D_2$ is abundantly produced in the brain and regulates the sleep response. Moreover, $PGD_2$ is a potential factor derived from P. falciparum within erythrocytes. Heme oxygenase-1 (HO-1) is catalyzing enzyme in heme breakdown process to release iron, carbon monoxide, and biliverdin/bilirubin, and may influence iron supply to the P. falciparum parasites. Here, we showed that treatment of a human astrocyte cell line, CCF-STTG1, with $PGD_2$ significantly increased the expression levels of HO-1 mRNA by RT-PCR. Western blot analysis showed that $PGD_2$ treatment increased the level of HO-1 protein, in a dose- and time-dependent manner. Thus, $PGD_2$ may be involved in the pathogenesis of cerebral malaria by inducing HO-1 expression in malaria patients.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.87-92
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• 2001

Carbon monoxide (CO) binds to soluble guanylate cyclase to lead its activation and elicits smooth muscle relaxation. The vascular tissues have a high capacity to produce CO, since heme oxygenase-2 (HO-2) is constitutively expressed in endothelial and smooth muscle cells, and HO-1 can be greatly up-regulated by oxidative stress. Moreover, the substrate of HO, heme, is readily available for catalysis in vascular tissue. Although the activation of heme oxygenase pathway under various stress conditions may provide a defence mechanism in compromised tissues, the specific role of HO-1-derived CO in the control of aortic contractility still remains to be elucidated. The present study was done to determine the effect of HO-1 induction on the aortic contractility. Thus, the effects of incubation of aortic tissue with S-nitroso-N-acetylpenicillamine (SNAP) for 1 hr on the aortic contractile response to phenylephrine were studied. The preincubation with SNAP resulted in depression of the vasoconstrictor response to phenylephrine. This effect was restored by HO inhibitor or methylene blue but not by NOS inhibitor. The attenuation of vascular reactivity by preincubation with SNAP was also revealed in endothelium-free rings. $AlF4^--evoked$ contraction in control did not differ from that in SNP-treated group. These results suggest that increased production of CO was responsible for the reduction of the contractile response to phenylephrine in aortic ring preincubated with SNAP and this effect of SNAP was independent on endothelium.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2004년도 Annual Meeting of KSAP : New Drug Development from Natural Products
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• pp.21-35
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• 2004

Heme oxygenase (HO)-l catabolizes heme into three products: carbon monoxide, bilirubin, and free iron. HO-l serves as a protective gene by virtue of the anti-inflammatory, anti-apoptotic and anti-proliferative actions of one or more of these three products. HO-l can be regarded as a potential therapeutic target in a variety of oxidant-mediated and inflammatory diseases. In this respect, it would be valuable to develop potent and selective inducers of HO-1 for therapeutic use. Here, we have shown that 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, catalposide and dehydrocostus lactone are potent inducers of HO-1 and exert cytoprotective and anti-inflammatory activities via HO-1-ependent machanism.

• 한국환경보건학회지
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• 제34권1호
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• pp.49-54
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• 2008

The induction of heme oxygenase-1(HO-1) by UV radiation provides a protective defence against oxidative stress, and has been well demonstrated in skin irradiated with UVA, but not UVB. In this study, we show that the induction of cutaneous HO-l can be attributed to UVB radiation. The expression of HO-1 mRNA was assessed in vivo by reverse transcription-polymerase chain reaction (RT-PCR) analysis, and HO-1 enzyme activity was measured in microsomal preparation from irradiated mice. The mRNA level of HO-1 increases in liver and skin from 1d to 3d after UVB $(3KJ/m^2)$ exposure. The results of gene expression were same pattern of HO-1 enzyme activity in skin, but not in liver. HO-1 mRNA in liver resulted in a progressive increase to 4d after UVB exposure, but HO-1 activity in liver increased to 2d. This finding indicates that UVB radiation is an important inducer of HO-1 and increases in HO activity may protect tissue directly or indirectly from oxidative stress.

• 한국환경성돌연변이발암원학회지
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• 제26권4호
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• pp.97-112
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• 2006

Heme oxygenase(HO)-1 is an important antioxidant enzyme that plays a pivotal role in cellular adaptation and protection in response to a wide array of noxious stimuli. Thus, HO-1 induction has been associated with prevention or mitigation of pathogenesis of various diseases, including acute inflammation, atherosclerosis, degenerative diseases, and carcinogenesis. Recent progress in our understanding of the function of molecules in the cellular signaling network as key modulators of gene transcription sheds light on the molecular mechanisms underlyuing HO-1 gene expression. A panel of redox-sensitive transcription factors such as activator protein-1, nuclear factor-kB, and nuclear factor E2-related factor-2, and some of the upstream kinases have been identified as prime regulators of HO-1 gene induction. This review summarizes molecular mechanisms underlying HO-1 expression and the significance of targeted induction of HO-1 as a potential chemopreventive or chemoprotective strategy.

• International Journal of Oral Biology
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• 제33권4호
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• pp.131-135
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• 2008

Substance P (SP) is known to be expressed in the nerve fibers of dental pulp and periodontal tissues. It was recently reported that SP expression increased in response to orthodontic force. In the present study, we investigated the effect of SP on expression of mineralization markers and heme oxygenase-1 (HO-1) in human immortalized periodontal ligament (IPDL) cells. Cell viability was measured using a 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay. The expression of mineralization markers, including alkaline phosphatase (ALP), osteonectin (ON) and bone sialoprotein (BSP), and heme oxygenase-1 (HO-1) was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. SP did not significantly change human IPDL cell viability, with the exception of the 24 hour treatment group. Treatment of human IPDL cells with $10^{-10}$ to $10^{-4}M$ SP upregulated mineralization marker and HO-1 expression in a time- and concentration-dependent manner. Our results suggest that SP may modulate osteoblastic cell differentiation of human IPDL cells through a mechanism involving HO-1 expression.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 KSOT/KEMS Fall Annual Meeting
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• pp.158-158
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• 2004

• 한국수정란이식학회지
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• 제30권4호
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• pp.305-313
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• 2015

Xenotransplantation of pig islet regarded as a good alternative to allotransplantation. However, cellular death mediated by hypoxia-reoxygenation injury after transplantation disturb success of this technique. In the present study, we produce transgenic pig expressing human heme oxygenase 1 (HO1) genes to overcome cellular death for improving efficiency of islet xenotransplantation. Particularly, Korean miniature pig breed, Micro-Pig, was used in the present study. Somatic cell nuclear transfer (SCNT) technique was used to produce the HO1 transgenic pig. Six alive transgenic piglets were produced and all the transgenic pigs were founded to have transgene in their genomic DNA and the gene was expressed in all tested organs. Also, in vitro cultured fibroblasts derived from the HO1 transgenic pig showed low reactive oxygen species level, improved cell viability and reduced apoptosis level.