• 제목/요약/키워드: Protoporphyrin

검색결과 116건 처리시간 0.039초

Analysis of Heme Biosynthetic Pathways in a Recombinant Escherichia coli

  • Pranawidjaja, Stephanie;Choi, Su-In;Lay, Bibiana W.;Kim, Pil
    • Journal of Microbiology and Biotechnology
    • /
    • 제25권6호
    • /
    • pp.880-886
    • /
    • 2015
  • Bacterial heme was produced from a genetic-engineered Escherichia coli via the porphyrin pathway and it was useful as an iron resource for animal feed. The amount of the E. coli-synthesized heme, however, was only few milligrams in a culture broth and it was not enough for industrial applications. To analyze heme biosynthetic pathways, an engineered E. coli artificially overexpressing ALA synthase (hemA from Rhodobacter sphaeroides) and pantothenate kinase (coaA gene from self geneome) was constructed as a bacterial heme-producing strain, and both the transcription levels of pathway genes and the intermediates concentrations were determined from batch and continuous cultures. Transcription levels of the pathway genes were not significantly changed among the tested conditions. Intracellular intermediate concentrations indicated that aminolevulinic acid (ALA) and coenzyme A (CoA) were enhanced by the hemA-coaA co-expression. Intracellular coproporphyrinogen I and protoporphyrin IX accumulation suggested that the bottleneck steps in the heme biosynthetic pathway could be the spontaneous conversion of HMB to coproporphyrinogen I and the limited conversion of protoporphyrin IX to heme, respectively. A strategy to increase the conversion of ALA to heme is discussed based on the results.

Gliotoxin Protects Trinitrobenzene Sulfonic Acid-Induced Colonic Damage through Induction of Heme Oxygenase-1

  • Oh, Jaemin;Hur, Jungmu;Kim, Yourim;Kwon, Young-Mi;Kim, Kyungsuk;Chung, Yeuntai;Choi, Minkyu
    • Toxicological Research
    • /
    • 제20권4호
    • /
    • pp.293-298
    • /
    • 2004
  • Background: Crohn's disease is characterized by a chronic relapsing inflammation of the bowel. Gliotoxin has been known to play strong immunosuppressive properties, while mechanisms for its anti-inflammatory actions are not completely understood. Here, we investigated the effects of gliotoxin in trinitrobenzene sulfonic acid (TNBS) induced mouse colitis, an animal model of Crohn's disease. Results: Gliotoxin dramatically improved clinical and histopathological symptoms in accompanied with reduced expression of TNF-$\alpha$, IL-1$\beta$, and ICAM-1 protein levels in TNBS induced colitis. Interestingly Gliotoxin induced Heme oxygenase-1 (HO-1) and the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) completely mimicked the protective effects of gliotoxin in TNBS induced colitis mice. In contrast, the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) could reverse the anti-inflammatory effects of gliotoxin and CoPPIX. Conclusions: Gliotoxin is a potential therapeutic agent targeting for the treatment of Crohn's disease by inducing HO-1.

Protoporphyrinogen Oxidase 저해형 제초제에 대한 밀과 보리의 Protoporphyrin IX축적 및 항산화 방어계 차이 (Difference of Protoporphyrin IX Accumulation and Antioxidative Activity of Wheat and Barley by Protoporphyrinogen Oxidase-Inhibiting Herbicides)

  • 국용인;구자옥;천상욱
    • 한국작물학회지
    • /
    • 제42권1호
    • /
    • pp.79-88
    • /
    • 1997
  • Protoporphyrinogen oxidase(Protox) 저해형 제초제로 알려진 oxyfluorfen(OF), acifluorfen(AF), bifenox(BF) 및 oxadiazon(OD)에 대해 밀이 보리보다 특이적으로 내성을 보인 요인이 이들 제초제 처리로 인하여 발생된 singlet oxygen을 무독화할 수 있는 항산화효소 및 항산화제의 능력 차이와 Protox 저해에 의한 protoporphyrin Ⅸ(PPIX)의 축적량에 기인하는지를 알아 보고자 하였다. 내성을 보인 밀과 감수성을 보인 보리에 OF, AF, BF 및 OD을 $10^{-6}$ M로 침지처리후 광에 2, 4, 6 및 8시간 경과후에 항산화효소 활성 변화를 본 결과, 이들 네 가지 약제 처리 후 monodehy-droascorbate reductase(MDAR), catalase(CAL) 및 superoxide dismutase(SOD)의 활성은 밀보다 보리에서 활성의 감소폭이 컸다. POX 활성은 OF 처리후 단지 8시간에만 밀보다 보리에서 활성이 적었을 뿐, 그밖의 AF, BF 및 OD 처리에서는 차이가 없었다. GR활성은 4약제 처리후 시간이 경과될수록 활성이 증가하였으나, 밀과 보리간에 활성의 차이는 없었다. 네 가지 약제 처리 후 항산화제인 vitamin C 함량은 밀보다 보리에서 함량 감소가 컸었다. Vitamin E는 OF처리에서만 밀이 보리보다 함량 감소가 적었을 뿐 그 밖의 약제에 대해서는 차이가 없었다. 그리고 carotenoid 함량은 AF처리에서만 밀이 보리보다 함량 감소가 적었을 뿐 그 밖의 약제에 대해서는 차이가 없었다 Glutathione(GSH, GSSG) 함량은 네 가지 약제처리 모두 밀보다 보리에서 함량이 많았다. 이들 약제 처리후 PPIX 축적량은 밀보다 보리에서 많았고, 특히 OF및 AF 처리에서는 각각 밀보다 보리에서 2.3배 및 1.3배가 더 많이 축적되었다.

  • PDF

납 사업장의 공기 중 납 농도 및 납 노출 근로자들의 납 관련 생물학적 노출 지표의 관련성에 관한 조사 (The Association of Lead Biomarkers of Lead Workers with Airborne Lead Concentration in Lead Industries)

  • 김남수;김진호;장봉기;김화성;안규동;이병국
    • 한국산업보건학회지
    • /
    • 제17권1호
    • /
    • pp.43-52
    • /
    • 2007
  • This study was designed to investigate the difference of airborne lead concentration by type of lead industries and type of lead exposure and to evaluate their association with lead biomarkers of lead workers in 11 lead using industries. Total of 182 lead workers (male: 167, female: 15) from 11 lead industries were participated for this study from March, 2004 to August, 2005. Airborne lead concentration were measured by representative personal sampling of workers in each unit workplace and applied same concentration value to the workers in the same unit workplace who did not measure their airborne lead with personal air sampling. Tibia lead, blood lead, zinc protoporphyrin in whole blood, ${\delta}$-aminolevulinic acid in urine, hemoglobin and hematocrit were selected as study variables of indices of lead exposure. Information about type of lead exposure (fume or non-fume other), age, work duration, smoking & drinking habit were also collected. Significant differences were seen in the means of zinc protoporphyrin, blood lead and tibia lead in lead workers by different airborne lead concentration in workplace. While blood lead and tibia lead in lead workers were significantly higher in secondary smelting than other types of lead industries, zinc protoporphyrin, ${\delta}$-aminolevulinic acid in urine and airborne lead concentration were significantly higher in litharge manufacturing. While the mean blood lead was significantly higher in the lead workers working in fume type unit workplace than those of non-fume lead workers, the mean airborne lead concentration of fume workers was significantly lower than non-fume lead workers. In the multiple regression analysis of airborne lead concentration and the type of lead exposure on tibia lead and lead exposure indices after adjustment of related covariates, airborne lead concentration was statistically significantly associated with blood lead and tibia lead, but the type of lead exposure was only associated with blood lead. To verify the causal association of airborne lead concentration on blood lead and tibia lead, further studies are needed.

류마티스 관절염에서 HO-1에 의한 VEGF 발현 유도에 대한 연구 (Effects of Heme Oxygenase-1 on VEGF Expression in Rheumatoid Arthritis)

  • 이승훈;권상철;변승재;장성조
    • 동의생리병리학회지
    • /
    • 제22권4호
    • /
    • pp.871-877
    • /
    • 2008
  • Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses and mediators of inflammation. HO-1 has been recently implicated in regulation of angiogenesis via expression of VEGF. The purpose of this study was to determine the effects of HO-1 modulation on the collagen-induced arthritis (CIA) model and on angiogenesis via up- regulation of VEGF expression in human synovial fibroblast. DBA/1J mice were treated with an inhibitor of HO-1, tin protoporphyrin IX (SnPP), or with an inducer of HO-1, cobalt protoporphyrin IX (CoPP), from day 1 to day 35 after CIA induction. The clinical evolution of disease was monitored visually. At the end of the experiment, histopathologic changes were examined on the joints. VEGF expression in paws were measured by immunohistochemical stain. mRNA expression of HO-1 and VEGF stimulated with various concentration of $TNF-{\alpha}$, CoPP accessed on human synovial fibroblast by RT-PCR. Effects of pretreatment with SnPP on mRNA expression of HO-1 and VEGF in the presence of CoPP and $TNF-{\alpha}$ in synovial fibroblast was accessed by Real-time RT-PCR. Administration of cobalt protoporphyrin IX significantly induced the inflammatory response, with increased arthritis index and expression of VEGF in the paws of the arthritis models. Treatment with SnPP significantly reduced the severity of CIA through inhibition of joint inflammation and cartilage destruction. The expression of VEGF were also significantly reduced by SnPP treatment in the paw. CoPPIX as inducer of HO-1, increased HO-1 and VEGF expression dose dependently in synovial fibroblast. In contrast, inhibition of HO-1 activity by SnPPIX abrogated CoPPIX-induced HO-1 and VEGF production in synovial fibroblast. Stimulation with $TNF-{\alpha}$ increased HO-1 and VEGF expression itself and showed additive effect on HO-1 and VEGF expression when it treated with CoPP. When SnPP was treated with CoPP and $TNF-{\alpha}$, it abrogated the CoPP induced HO-1 and VEGF expression and also abrogated $TNF-{\alpha}$ induced HO-1 and VEGF expression in synovial fibroblast. The effects of HO-1 induction in rheumatoid arthritis results in aggravation of arthritis via up-regulation of VEGF. I concluded that inhibition of the expression or activity of HO-1 could be a therapeutic target of rheumatoid arthritis.

연 폭로시 성별에 따른 혈중 Zinc Protoporphyrin의 양-반응 관계 (Different Effect of Blood Lead on Zinc Protoporphyrin by Gender in Korean Lead Workers)

  • 김용배;리갑수;황규윤;이성수;안규동;이병국;안현철
    • Journal of Preventive Medicine and Public Health
    • /
    • 제32권4호
    • /
    • pp.499-504
    • /
    • 1999
  • Objectives : To evaluate whether a relation between blood lead and zinc proto porphyrin(ZPP) was modified by gender in Korean lead workers. Methods : A cross-sectional study was conducted with 1,304 male and 101 female subjects in 1997. The relation between blood lead and ZPP were evaluated with linear, exponential, and quadratic models. Then, the different effect of gender on the relation was examined by adding the interaction terms in the each model. Results : $Mean{\pm}SD$ of blood lead and ZPP level was different between male$(27.7{\pm}10{\mu}g/dl\;and\;51.3{\pm}23.4{\mu}g/dl)$ and female subjects$(22.5{\pm}9.2{\mu}g/dl\;and\;78.7{\pm}38.6{\mu}g/dl)$. After adjusting for possible confounders, the effect modification by gender was significant in linear$(\beta=1.119,\;p<0.001)$, exponential$(\beta=Exp(0.008),\;p<0.05)$, and quadratic model$(\beta=1.388,\;p<0.001)$. In separate analysis, a quadratic relation between blood lead and ZPP was shown in male lead workers$(\beta=0.036,\;p<0.001)$, but an exponential relation in female lead workers$(\beta=Exp(0.029), p<0.001)$. Conclusion : Our data showed that the increasing rate of ZPP in female were always higher than in male lead workers, suggesting that females were more susceptible to occupational lead exposure than males.

  • PDF

A Strategy Using Photodynamic Therapy and Clofibric Acid to Treat Peritoneal Dissemination of Ovarian Cancer

  • Yokoyama, Yoshihito;Shigeto, Tatsuhiko;Miura, Rie;Kobayashi, Asami;Mizunuma, Makito;Yamauchi, Aisa;Futagami, Masayuki;Mizunuma, Hideki
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제17권2호
    • /
    • pp.775-779
    • /
    • 2016
  • Background: The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. Materials and Methods: Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. Results: Rats receiving methyl-ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. Conclusions: The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.

Interaction of Cytochrome c and $Mn^{2+}$ -Cytochrome c Peroxidase

  • Kim, Mun-kyoung;M. Kwon;Kim, K.;Sanghwa Han
    • 한국생물물리학회:학술대회논문집
    • /
    • 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
    • /
    • pp.44-44
    • /
    • 1999
  • Yeast cytochrome c peroxidase (CcP) was cloned and overexpressed in E. coli, and purified by a Ni$^{2+}$-affinity column. HoloCcP was obtained by reconstituting apoCcP with Mn$^{3+}$-protoporphyrin IX (MnPP). Electron paramagnetic resonance (EPR) spectra of spin-labeled holoCcP showed a slightly more immobilized signal than spin-labeled apoCcP.(omitted)

  • PDF