• Clinical and Experimental Reproductive Medicine
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• 제28권2호
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• pp.131-140
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• 2001

Objective: To know the effects of xenoestrogen on spermatogenesis, we investigated the expression of cytochrome P450s enzymes (CYPscc, $CYP_{17{\alpha}}$, CYP19) and $3{\beta}$-HSD genes involved in steroidogenesis. Methods: Mouse testicular cells were prepared from 15-day-old ICR mice which had only pre-meiotic germ cells by enzyme digestion using collagenase and trypsin. Testicular cells were cultured in DMEM supplemented with FSH (0.1 IU/ml) and 10% FBS or medium with estrogen ($E_2$), bisphenol-A (BPA), octylphenol (OP; $10^{-9},\;10^{-7},\;10^{-6},\;10^{-5},\;10^{-4}M$, respectively) and aroclor 1254 (A1254) known as PCBs for 48 hours. The gene expression of cytochrome P450 enzymes were examined by semi-quantitive RT-PCR. The production of estrogen and testosterone was examined by RIA. Results: As results, expression of CYPscc mRNA was not significantly decreased, but $3{\beta}$-HSD and $CYP_{17{\alpha}}$. mRNA were significantly dose-dependent decreased. And production of testosterone and estrogen were not different except BPA and OP group ($10^{-5}M$). Conclusion: BPA, OP and A1254 might inhibit steroidogenesis by decreasing CYPscc, $3{\beta}$-HSD and $CYP_{17{\alpha}}$. mRNA expression in the mouse testis. These results suggest that BPA, OP and PCBs like as an endocrine disruptors inhibit the productions of steroidogenic enzymes and decrease the production of T and E by negative feedback mechanism. Therefore, these might disrupt steroidogenesis in Leydig cells of testis and would disturb testicular function and subsequently impair spermatogenesis.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.195-197
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• 2007

Currently praziquantel is used for treatment of not only clonorchiasis but also other trematodes and cestodes. But cure rate of praziquantel is just 60-80% for most trematodes. It needs for the treatment-failed patients to have more drugs. The cause of failure of treatment is not studied. We just know that the blood level of praziquantel is severely different among the people. We guess that this factor may influence the results of treatment. In an endemic area of human clonorchiasis in Heilongjiang Providence, China, 78 subjects were selected for the study. Three doses of 25 mg/kg (total 75 mg/kg) of praziquantel were administered to 78 clonorchiasis patients. After three weeks of treatment, stool examination was undertaken once again to confirm the cured and uncured subjects. To analyze SNP (single nucleotide polymorphism) of CYP3A5 PS2-1, CYP3A5 PS2-2, and CYP3A5*6, PCR method was done with specifically designed primers. The mutation rates of all sites were not significant statistically. The number of subjects was too small, so we need more subjects and other delivery proteins of bile ducts (ex. MRP etc.) were also considered for effects of praziquantel. We analyzed, for the first time, the entire CYP3A5 gene in a French population, using a polymerase chain reaction- single strand conformational polymorphism (PCR-SSCP) strategy.

• Toxicological Research
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• 제24권2호
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• pp.109-112
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• 2008

The G184C and G134A single nucleotide polymorphisms(SNPs) of the CYP1A1 gene result in Ala62Pro and Gly45Asp substitutions, respectively. Here, we tested whether these SNPs are associated with an alteration in lung cancer incidence. We examined 80 Korean subjects with lung cancer and 240 age- and sex-matched controls. For each subject, the CYP1A1 gene was PCR amplified and sequenced. We observed that the odds ratio(OR) for lung cancer was 3.37 higher in subjects with the G184C polymorphism than in controls(95% confidence interval(CI), $0.89{\sim}12.73$, P=0.07). In contrast, the OR for lung cancer was 1.23 in subjects with the G134A polymorphism compared to controls(95% CI, $0.68{\sim}2.20$, P=0.49). The G184C polymorphism exacerbated the effects of smoking on lung cancer development. Gene-smoking interaction analyses revealed that past or present smokers with the G184C polymorphism had a higher incidence of lung cancer(OR, 24.72; 95% CI, $4.48{\sim}136.31$; P<0.01) than control smokers(OR, 6.65; 95% CI, $2.72{\sim}16.28$; P<0.01). However, there was only a slight difference in the ORs for lung cancer between control smokers and smokers with the G134A polymorphism. These findings suggest that the G184C polymorphism, but not the G134A polymorphism, is associated with an increased risk of lung cancer.

• 한국균학회지
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• 제42권4호
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• pp.282-288
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• 2014

본 연구에서는 순창지역에서 만들어지는 장류에서 곰팡이를 분리하고 동정하여 보다 안전하고 기능성이 높은 발효제품을 위한 균주를 확보하고자 하였다. 순창지역에서 생산되는 장류 제품으로부터 곰팡이를 분리하여 ${\beta}$-tubulin 유전자 분석 통해 10개의 균주가 Aspergillus oryzae/flavus complex임을 알 수 있었다. 보다 정확한 동정을 위하여 아플라톡신 클러스터 유전자 중에 하나인 omtA의 염기서열을 증폭하여 A. oryzae와 A. flavus 표준 균주의 omtA 서열과 함께 계통 분류한 결과, A. oryzae의 표준 균주와의 유연관계가 높음을 알 수 있었다. 또한 norB-cypA 사이의 염기서열을 증폭한 결과 500 bp이 증폭 산물이 확인되었는데 이는 표준 균주인 A. oryzae의 norB-cypA 사이의 염기서열 증폭 산물과 동일한 크기임을 확인할 수 있었다. A. oryzae로 확인된 10균주를 활용하여 코지를 제조하고 ${\alpha}$-amylase 활성과 protease 활성을 측정하였다. Protease 활성은 6, 13, 17, 27, 37, 그리고 38 균주로 제조된 코지는 대조구(시판되고 있는 종균으로 제작한 코지)보다 2배 정도 높은 protease 활성을 보였으며, ${\alpha}$-amylase 활성은 257~320 U/mL로 측정되었다. 식품안전성을 위한 아플라톡신 분비 확인 결과, 63번 균주로 제조된 코지를 제외한 모든 코지에서 아플라톡신을 만들지 않는 것으로 확인되어, 순창에서 분리된 A. oryzae는 추후 메주 접종균으로 개발할 수 있음을 보여주었다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2711-2715
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• 2012

Background: Bisphenol A (BPA), an endocrine disrupting chemical, has been suspected to pose carcinogenic risks. However, likely mechanisms are obscure and there are difficulties to estimating its real significance for cancer development. Methods: We therefore studied BPA-induced proteomic alterations in immune organs of ICR mice offspring that were prenatally exposed to BPA (15 and 300 mg/L of drinking water). We performed 2D-gel analyses of samples, considering differences in spleen, exposure levels, sex, and ages. Results: From proteomic analyses, we found various proteins were up- or down-regulated by BPA. Among them, SET, a putative oncogene and inhibitor of phosphatase 2A, was significantly down-regulated in a BPA dose-dependent manner. We also confirmed down-regulation of SET in western blot and real time PCR analyses. From gene network analysis, SET is predicted to communicate with other genes including CYP17, which is involved in biosynthesis and metabolism of sex-hormones. Conclusions: This study provided evidence that SET can be applied as a new biomarker for prenatal BPA exposure and suggests a potential new mechanism of action in that BPA may disrupt CYP17 via SET.

• Parasites, Hosts and Diseases
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• 제60권1호
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• pp.39-43
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• 2022

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.134-144
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• 2019

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

• Journal of Ginseng Research
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• 제44권6호
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• pp.757-769
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• 2020

Background: Panax quinquefolius and Panax notoginseng are widely used and well known for their pharmacological effects. As main pharmacological components, saponins have different distribution patterns in the root tissues of Panax plants. Methods: In this study, the representative ginsenosides were detected and quantified by desorption electrospray ionization mass spectrometry and high-performance liquid chromatography analysis to demonstrate saponin distribution in the root tissues of P. quinquefolius and P. notoginseng, and saponin metabolite profiles were analyzed by metabolomes to obtain the biomarkers of different root tissues. Finally, the transcriptome analysis was performed to demonstrate the molecular mechanisms of saponin distribution by gene profiles. Results: There was saponin distribution in the root tissues differed between P. quinquefolius and P. notoginseng. Eight-eight and 24 potential biomarkers were detected by metabolome analysis, and a total of 340 and 122 transcripts involved in saponin synthesis that were positively correlated with the saponin contents (R > 0.6, P < 0.05) in the root tissues of P. quinquefolius and P. notoginseng, respectively. Among them, GDPS1, CYP51, CYP64, and UGT11 were significantly correlated with the contents of Rg1, Re, Rc, Rb2, and Rd in P. quinquefolius. UGT255 was markedly related to the content of R1; CYP74, CYP89, CYP100, CYP103, CYP109, and UGT190 were markedly correlated with the Rd content in P. notoginseng.

• 대한의생명과학회지
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• 제18권1호
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• pp.1-9
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• 2012

Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.

• Nutrition Research and Practice
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• 제7권4호
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• pp.287-293
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• 2013

This study determined the effects of fucoxanthin on gene expressions related to lipid metabolism in rats with a high-fat diet. Rats were fed with normal fat diet (NF, 7% fat) group, high fat diet group (HF, 20% fat), and high fat with 0.2% fucoxanthin diet group (HF+Fxn) for 4 weeks. Body weight changes and lipid profiles in plasma, liver, and feces were determined. The mRNA expressions of transcriptional factors such as sterol regulatory element binding protein (SREBP)-1c, Carnitine palmitoyltransferase-1 (CPT1), Cholesterol $7{\alpha}$-hydroxylase1 (CYP7A1) as well as mRNA expression of several lipogenic enzymes were determined. Fucoxanthin supplements significantly increased plasma high density lipoprotein (HDL) concentration (P < 0.05). The hepatic total lipids, total cholesterols, and triglycerides were significantly decreased while the fecal excretions of total lipids, cholesterol, and triglycerides were significantly increased in HF+Fxn group (P < 0.05). The mRNA expression of hepatic Acetyl-CoA carboxylase (ACC), Fatty acid synthase (FAS), and Glucose-6-phosphate dehydrogenase (G6PDH) as well as SREBP-1C were significantly lower in HF+Fxn group compared to the HF group (P < 0.05). The hepatic mRNA expression of Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and Acyl-CoA cholesterol acyltransferase (ACAT) were significantly low while lecithin-cholesterol acyltransferase (LCAT) was significantly high in the HF+Fxn group (P < 0.05). There was significant increase in mRNA expression of CPT1 and CYP7A1 in the HF+Fxn group, compared to the HF group (P < 0.05). In conclusion, consumption of fucoxanthin is thought to be effective in improving lipid and cholesterol metabolism in rats with a high fat diet.