• 셀메드
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• 제3권1호
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• pp.1.1-1.7
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• 2013

The present review investigates the role of the cytoprotective enzyme heme oxygenase-1 (HO-1) in human diseases and explores strategies for its clinical use. In recent years, there has been a growing evidence, for the beneficial effects of some phytoconstituents via induction of HO-1 expression, contained in commonly used spices, fruits, and herbs, in preventing various pathologic conditions, including cancer, diabetes, and cardiovascular diseases. HO-1 catalyzes the rate-limiting step in heme catabolism to generate ferrous iron, carbon monoxide, and biliverdin. HO-1 is reported to play crucial roles in cellular protection, such as anti-inflammatory, anti-proliferative and anti-apoptotic effects. These evidences indicate that HO-1 may functions as a potential therapeutic target in various human diseases. The article highlights the current status of the development of the HO-1 modulation pathway using dietary phytoconstituents.

• Archives of Pharmacal Research
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• 제26권5호
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• pp.411-415
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• 2003

To investigate the mechanisms involved in hemin-induced febrile response, the rectal temperature of rats were measured after intracerebroventricular (i.c.v.) injections of hemin, with or without antagonists. Hemin ($10\mu\textrm{g}$) elicited a significant febrile response, which lasted from 30 min, to more than 6 h, after its administration, but this was not the case with biliverdin (i.c.v.) and bilirubin (i.c.v.). The hemin-induced febrile response was significantly inhibited by pretreatment with an inhibitor of tyrosine kinase (genistein), but not by pretreatment with an inhibitor of protein kinase C (chelerythrine) and a scavenger of iron (deferoxamine). These results suggest that tyrosine kinase is involved in the hemin-induced febrile response.

• KSBB Journal
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• 제20권1호
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• pp.21-25
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• 2005

흔하게 사용되어온 제초제인 paraquat는 파킨슨병의 원인이 될 수 있는 유력한 위험 요소이다. 헴산화효소-1(HO-1)은 산화적 스트레스와 소포체 스트레스의 marker인데, 여러 가지 자극에 의해 heme을 분해하여 biliverdin, 일산화탄소, 철 성분으로 전환시킨다 본 연구에서는 뇌의 흑색질 유래의 도파민 세포주 SN4741에서 paraquat가 시간별, 농도별로 HO-1을 활성화시키는 기작을 조사하였다. HO-1이 Paraquat에 의해 활성화되는 것은 주로 유전자 전사 수준에서 조절되었다. HO-1 유전자의 promoter와 5' enhancer인 El, E2를 결실시킨 실험에서, E2 enhancer가 도파민 세포에서 paraquat에 의한 HO-1 유전자 발현을 유도하는 핵심 부위로 판명되었다 E2 enhancer 부위를 돌연변이 시킨 실험 결과는 전사인자 활성 단백질-1 (AP-1) 결합부위를 통해 HO-1 발현이 유도됨을 밝히게 되었다. 또한, 도파민 세포에서 HO-1 유전자 발현의 조절과 신호전달 과정의 관계를 조사하기 위해 MAP kinase들의 특이적 저해제를 처리하고 paraquat로 자극을 준 결과, JNK 저해제인 SP600125가 가장 현저하게 paraquat에 의한 HO-1 발현을 억제하였다. 결론적으로, 도파민 세포에서 paraquat가 HO-1을 유도하는 데는 E2 enhancer가 중요하게 작용하고, AP-1과 JNK 경로를 통해 HO-1 발현이 조절된다는 사실을 처음으로 밝히게 되었다.

• 한국가금학회지
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• 제27권2호
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• pp.115-132
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• 2000

본 장에서는 양질의 계란생산에 필요한 난각과 난각색의 형성에 관해서 언급하였다. 강한 난각의 형성은 난각을 이루는 내적인 요인들 (큐티클층, 진각, 난각층의 조직)과 소화기, 난각형성에 관여하는 각종 체내 분비선, 신장, 호르몬 등의 적정기능에 의하여 결정된다. 병아리가 성성숙에 달하면 골수골은 산란계가 난각의 형성이 정점에 달했을 때를 대비 할 수 있는 정도가 되어야 한다. 난각이 형성되는데 중요한 기능을 갖는 요인들로는 산란계 사료중의 칼슘원, 산란계사료 중의 칼슘과 인의 비율, 비타민 D의 적정수준, 체액중의 각종 무기물 균형, 기타 영양소 수준들을 들 수 있다. 또 생리적, 환경적인 요인들과 산란계의 나이나 산란계사의 온도와 습도, 산란계의 계통, 질병, 계사에서 알의 수집부터 수송에 이르기까지의 각종 관리형태 등은 계한이 생산자에서부터 소비자에 이르기까지 여러 단계에서 나타나는 각종 난각 파괴의 요인이 된다. 난각에 나타나는 색소에 관여되는 요인들로는 protoporphyrin-IX, biliverdin-IX, 아연 등이 함유된 킬레이트와 때로 적은 양이 관여하기는 하지만 coproporphyrin-III 등이 포함된다. 그러나 이러한 요인들이 난각색의 형성에 관여하는 데에는 산란계의 연령, 질병, 약품 첨가 여부, 난각 형성도 중 난각 표면의 손상 여부 등 여러 가지가 관여된다.

• Animal cells and systems
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• 제3권2호
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• pp.173-180
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• 1999

A blue biliprotein, insecticyanin (INS), has been purified from the last instar larval hemolymph of Agrius convolvuli by ultracentrifugation, Sephadex G-100 gel permeation chromatography, and preparative electrophoresis. The molecular mass of INS was estimated to be 26 kDa and the N-terminal sequence of INS revealed high similarity to that of Manduca sexta. Results of Western blotting and autoradiography indicated that INS is synthesized by the epidermis and released into the hemolymph. In contrast to the INS reported in other insects, Agrius convolvuli INS contained a small amount of lipid, predominately consisting of triacylglycerol. Subcellular localization of INS was determined using protein-A gold particles linked to secondary antibodies (anti-rabbit Ig). INS was heavily accumulated in the cytoplasmic inclusion body (CIB). CIBs showed a variety of shapes from rod to globule and generally surrounded the nucleus. They were mostly located near the basement membrane and especially abundant in the intersegmental membrane.

• 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.

• BMB Reports
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• 제39권5호
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• pp.479-491
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• 2006

Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.

• 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.

• 대한화학회지
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• 제37권7호
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• pp.672-676
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• 1993

DMF 용액 중에서 zinc(II) 이온과 copper(II) 이온의 bilirubin과의 착물형성 여부를 조사하고 Zn(II)-bilirubin(이하 Zn(II)-BR로 줄임) 착물의 전기화학적 성질을 여러가지 전기화학적인 방법으로 조사하였다. Zn(II)는 DMF 용액 중에서 bilirubin과 착물을 형성하였으나, Cu(II)는 bilirubin과 착물을 형성하지 않고 오히려 bilirubin의 산화를 촉진시켰다. Zn-BR 착물은 3단계의 환원과정을 거치며, 제1파와 제2파의 환원전류는 반응성 전류가 약간 포함된 환산전류이었으며, 제3파의 환원전류는 확산지배적인 전류이었다.

• Molecules and Cells
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• 제39권6호
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• pp.460-467
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• 2016

Bacteriophytochromes are phytochrome-like light-sensing photoreceptors that use biliverdin as a chromophore. To study the biochemical properties of the Deinococcus radiodurans bacteriophytochrome (DrBphP) protein, two anti-DrBphP mouse monoclonal antibodies (2B8 and 3H7) were generated. Their specific epitopes were identified in our previous report. We present here fine epitope mapping of these two antibodies by using truncation and substitution of original epitope sequences in order to identify minimized epitope peptides. The previously reported original epitope sequences for 2B8 and 3H7 were truncated from both sides. Our analysis showed that the minimal peptide sequence lengths for 2B8 and 3H7 antibodies were nine amino acids (RDPLPFFPP) and six amino acids (PGEIEE), respectively. We further characterized these peptides in order to investigate their reactivity after single deletion and single substitution of the original peptides. We found that single-substituted 2B8 epitope (RDPLPAFPP) and dual-substituted 3H7 epitope (PGEIAD) showed significantly increased reactivity. These two antibodies with high reactivity for the short modified peptide sequences are valueble for developing new peptide tags for protein research.