• Journal of Microbiology and Biotechnology
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• v.25 no.6
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• pp.880-886
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• 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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.8 no.2
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• pp.263-268
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• 2005

Erythropoietic protoporphyria is a genetic disorder due to a deficiency of ferrochelatase resulting in excessive accumulation and excretion of protoporphyrin. The predominant clinical feature is photosensitivity. Severe hepatic failure occurs in a small percentage of patients, and neurological symptoms are very rare. We report a case of erythropoietic protoporphyria associated with severe hepatic dysfunction and neurological symptoms. A 9-year-old girl presented with severe abdominal pain, nausea, weakness and pain of extremities, and urinary retention. Ultrasonogram and abdominal CT scanning revealed a diffuse infiltrated and enlarged liver. Liver biopsy showed deposition of dense dark brown pigment within the bile, hepatocytes and Kupffer cells. Plus, dense dark brown deposits gave a red birefringent under polarize light. Porphyrin studies demonstrated markedly elevated serum free erythrocyte protoporphyrin. This girl was diagnosed as erythropoietic protoporphyria with severe liver dysfunction and neurological symptoms.

• Toxicological Research
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• v.20 no.4
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• pp.293-298
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• 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.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.42 no.1
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• pp.79-88
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• 1997

This experiment was conducted to investigate the protoporphyrin Ⅸ (PPIX)accumulation, activity of antioxidative enzymes and contents of antioxidant in tolerant-wheat and susceptible-barley to protoporphyrinogen oxidase (Protox) inhibiting-herbicides [oxyfluorfen(2-chloro-l-(3-ethoxy-nitrophenoxy-4-(trifluoromethyl) benzene, acifluorfen (5-[2-chloro-4-(trifl-uoromethyl) phenoxy]-2-nitrobenzoic acid), bifenox(methyl-5-(2, 4-dichlorophenoxy) 2-nitroben-zoate), and oxadiazon (5-tert-butyl-3-(2,4-dichloro-5-isopropoxyphenyl)-1,3,4-oxadiazol-2-one)]. The tolerant-wheat and susceptible-barley were soaked in these compounds at 10$^{-6}$ M for 2hrs and exposed to light for 2,4,6 or 8hrs to investigate change of the activity of antioxidative enzymes. The activities of monodehydroascorbate reductase(MDAR), catalase(CAL) and superoxide dismutase(SOD) were lower in the barley than in the wheat after the treatement of these compounds. The activity of peroxidase(POX) was lower in the barley than in the wheat at 8hrs after the treatment of oxyfluorfen but other compounds showed no difference in activity in wheat and barley. The activity of glutathione reductase(GR) was increased in wheat and barley according as hours of treatment of these compounds became increased but its activity was no difference between wheat and barley. In the case of the content of vitamin C due to the treatment of these compounds, the wheat decreased less than the barley. After the treatment of oxyfluorfen the content of vitamin E in the wheat was higher than in the barley but other compounds didn't have any difference between wheat and barley. And after the treatment of acifluorfen the content of carotenoid was greater in the wheat than in the barley but other compounds didn't have any difference between wheat and barley. The content of glutathione (GSH, GSSG) was greater in the barley than in the wheat. The content of protoporphyrin Ⅸ (PPIX) accumulation by the treatments of these compounds was more in the barley than in the wheat. Especially, the treatment of oxyfluorfen and acifluorfen were more accumulated 2.3 and 1.3 fold in the barley than in the wheat, respectively.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.17 no.1
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• pp.43-52
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• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.871-877
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• 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.

• Journal of Preventive Medicine and Public Health
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• v.32 no.4
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• pp.499-504
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• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.775-779
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• 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.

• Proceedings of the Korean Society of Life Science Conference
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• 2006.09a
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• pp.115.1-115.1
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• 2006

• Proceedings of the Korean Biophysical Society Conference
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• 1999.06a
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• pp.44-44
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• 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)