• Journal of Life Science
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• v.34 no.3
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• pp.199-207
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• 2024

Cytochrome P450s (CYP) enzymes play a central role in the metabolism of both endogenous and xenobiotic chemical compounds. In particular, therapeutic drugs, natural products and environmental toxicants regulate expression of the tissue-specific CYP enzymes, This can cause CYP-mediated interactions among the chemical compounds such as the ingested drugs and toxicants, resulting in changes in their metabolism. This can lead to the modifications of their therapeutic and toxic effects. Intense investigations in this field throughout the last several decades have resulted in considerable progress in understanding the molecular mechanisms mediating the regulation of CYP gene expression. Now, it is well established that xenobiotic chemicals regulate the expression of specific CYP genes, and the corresponding xenobiotic-sensing receptors that mediate the expression control of specific CYP genes and their signal transduction pathways are involved in this process. This review summarizes the molecular mechanisms by which the well-known major xenobiotic-sensing receptors and other regulators affect the induction of CYP gene expression in response to exposure to various chemicals.

• Journal of Life Science
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• v.34 no.7
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• pp.465-475
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• 2024

Lactiplantibacillus plantarum K9 is a probiotic strain that can be utilized from various bioactive substances isolated from Protaetia brevitarsis seulensis larvae. In this study, a genetic analysis of L. plantarum K9 revealed the existence of a bacterial chromosome and three plasmids. The glycolysis pathway and pentose phosphate pathway were examined for their normal functioning via an analysis of the core metabolic pathways of L. plantarum K9. Since the key enzymes, fluctose-1,6-bisphospatase (EC: 3.1.3.11) and 6-phosphogluconate dehydratase (EC: 4.2.1.12)/2-keto-deoxy-6-phosphogluconate (KDPG) aldolase (EC: 4.2.1.55), of gluconeogenesis and the ED pathway were not identified from the L. plantarum K9 genome, we suggest that gluconeogenesis and the ED pathway are not performed in L. plantarum K9. Additionally, while some enzymes, related to fumarate and malate biosyntheses, involved in the TCA cycle were identified from L. plantarum K9, the enzymes associated with the remaining TCA cycle were absent, indicating that the TCA cycle cannot proceed. Meanwhile, based on our findings, we propose that the oxidative electron transport system performs class IIB-type (bd-type) electron transfer. In summary, we assert that L. plantarum K9 performs homolactic fermentation, executes gluconeogenesis and the pentose phosphate pathway, and carries out energy metabolism through the class IIB-type oxidative electron transport system. Therefore, we suggest that L. plantarum K9 has relatively high lactic acid production, and that it has excellent antibacterial activity, as a result, compared to other lactic acid bacterial strains. Moreover, we speculate that L. plantarum K9 has an oxidative electron transport capability, indicating that it is highly resistant to oxygen and suggesting that it has fine cultivation characteristics, which collectively make it highly suitable for use as a probiotic.

• Journal of the korean veterinary medical association
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• v.25 no.10
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• pp.595-606
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• 1989

항원제시세포(APC)와 보조T세포 간의 협력작용에 의하여 활성화된 작동세포(NK세포, CTL, K세포, 대식세포, 과립구 등)의 종양세포, 이식장기 및 세포내기생세균에 감염된 각종 세포에 대한 세포독성작용은 생체방어를 위한 중요한 세포성면역기전이다. 지난 몇 년간 세포성면역기전에 관한 많은 연구에도 불구하고 T림파구매개성 세포독성작용의 면역생물학적기전은 확실히 밝혀있지 않다. 지금까지 알려진 중요한 연구내용을 요약하면 다음과 같다. 1. 세포독성작용을 나타내는 작동세포로는 NK세포, CTL, K세포, 대식세포/단핵구 및 과립구가 있다. 2. T세포의 세포표면항원분자군(CD)으로는 $CD_{2},\;CD_{3},\;CD_{4}[Ly_{3}T_{4}],\;CD_{5}[=Ly_{1}],\;CD_{7},\;CD_{8}[Ly_{2,3}]$가 있으며 $CD_{4}$는 보조Ttpvhdml 특이마커이고 $CD_{8}$는 세포독성 T세포 및 억압T세포의 특이마커이다. 주요 T세포수용체(TCR)는 $CD_{4}$ 또는 $CD_{8}$ 분자와 가까이 연합된 이향체($TCR-{\alpha}{\beta}/TCR-{\gamma}{\delta}$이며 보조 T세포 $CD_{4}$(마우스 $L_{3}T_{4}$)는 수용체와 연합되어 있는반면 억압 T세포 $CD_{8}(Ly+_{2,3})$는 항원수용체와 연합되어 있다. 3. T세포는 Ti-$CD_{3}$(항원/MHC) 복합체를 통한 '항원가교'에 의한 자극(항원인식)과 $CD_{2}$를 통한 비특이경로에 의하여 활성화(분화증식)된다. 비특이경로를 통한 활성경로에서 T세포($CD_{4}$ 및 $CD_{8}$)가 활성화되기 위하여는 보조T세포가 생산하는 IL-2을 요구하며 IL-2의 자극으로 분화증식된 $CD_{8}$는 세포독성능을 나타내지만 $CD_{4}^{+}$는 여전히 세포독성능을 나타내지 못한다. 4. 보조T세포는 class II MHC분자와 연합된 항원을 식별하는 반면 세포독성T세포는 class I MHC 분자와 연합된 항원을 식별한다. 5. 림파구 매개성 세포독성은 접촉(conjugati-on), 탈분극(depolarization), 용해계획(progra-mming), 용해(lysis) 및 재순환(recycling)의 단계를 거쳐 진행된다. 6. 표적세포살해매체로는 perforin / PFP / cy-tolysin, lymphopores, lymphotoxins, protone, cytolytic enzymes가 알려졌으며 세포독성작용은 이들 이외에도 여러 가지 매체를 통한 복합작용으로 추정된다. 7. CTL 매개성 표적세포의 주요 대사변화는 actomyocin ATPase의 증가, phosphocreatine과 ATPase의 소모, ATP 의존성 $Na^{+}/K^{+}$ 펌프작용의 중지, ATP 의존성 $Ca^{2+}$ 유출감소 및 세포내 축적이 관찰된다. 8. $Ca^{2+}$의 축적으로 세포막 교질 침투손상을 주어 수분의 유입을 증가시킴으로써 수포형성, 핵붕괴, 사립체팽화 및 정상세포 구조상실(Zeiosis)이 있다. 결론적으로 CTL 매개성 세포독성작용은 PFP, LT, TNF, 유사 TNF / LT 및 기타 매체를 통한 복합작용이며 세포살해기전은 지속적 대사소모와 정형적 세포구조(핵 및 세포질)의 파괴에 의한 것이다.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.8
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• pp.1273-1278
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• 2004

The change of tissue lipid levels and fatty acid compositions in alloxan-induced diabetes was studied in rats (SD, male) in order to examine the pathway of diabetic complications. Rats were injected with alloxan 20 mg/kg BW or 40 mg/kg BW to induce diabetes. In rats injected with alloxan (40 mg/kg BW), the body weight was significantly decreased, food intake and liver weight per 100 g (BW) were significantly increased, compared with other groups. The blood glucose levels were apparently elevated as about 2 times in rats injected with alloxan (40 mg/kg BW) than the other groups. The concentrations of serum total cholesterol, triglyceride and HDL-cholesterol were not significantly different among the groups. However, the levels of serum triglyceride tended to increase according to amount of alloxan injected. Liver cholesterol levels were significantly decreased in rats injected with alloxan (40 mg/kg BW) compared with other groups, but triglyceride levels of those were not significantly different among groups. Concerning the fatty acid compositions of serum, liver, kidney, spleen phosphatidylcholine, the percentage of linoleic acid in rats injected with alloxan (40 mg/kg BW) was significantly increased, while that of arachidonic acid was significantly decreased compared with the other groups. Therefore, the ratios of arachidonic/linoleic acid in tissue phosphatidylcholine tended to be low in rats injected with alloxan (40 mg/kg BW) and especially significant low levels were found in serum and spleen. Thus, it was suggested that insulin deficiency can affect on fatty acid biosynthesis and induce diabetic complications.

• Applied Biological Chemistry
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• v.26 no.2
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• pp.97-103
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• 1983

To get further information on the behavior of phorate(0,0-diethyl S-ethylthiomethyl phosphorodithioate) in soil under the subtropical conditions, a field experiment has been conducted. Phorate granule (10%) was applied to silt loam soil at the rate of 40kg a.i./ha and incorporated to 10cm soil depth. Residues of phorate and its metabolites in soil were determined with GLC and confirmed qualitatively with TLC. Phorate was rapidly oxidized to its sulfoxide and sulfone. Therefore, main metabolic pathway of phorate in soil was the oxidation of phorate to phorate sulfoxide and sulfone. Phorate sulfoxide and sulfone were relatively more persistent than phorate itself. Phoratoxon was detected at low level only up to 30 days after treatment and its sulfoxide and sulfone were not detected during the whole experimental period. Toluene-acetonitrile-nitromethane(40 : 30 : 30, v/v/v) solvent system separated satisfactorily phorate and its five metabolites. Most of the residues was found in the initial incorporation depth $(0{\sim}10cm)$. Consequently, insecticides showed a little downward movement.

• Journal of Nutrition and Health
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• v.12 no.1
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• pp.9-16
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• 1979

Cholecalciferol은 피하에서 자외선과 체온의 작용을 받아 7-dehydrocholesterol로부터 Previtamin D를 거쳐 합성이 되며 이어서 간에 빨리 축적, 25 hydroxylation을 거치게 되고 신장에서 가장 활성을 띤 형태인 $1.25-(OH)_{2}CC$로 변하게 된다. 한편 신장에서는 체내의 Ca, P이 정상으로 존재하게 되면 1-hydroxylation이 억제되는 대신 24-hydroxylation이 일어나 또 다른 active form인 $24,\;25-(OH)_{2}CC$가 되는데 24-hydroxylation의 역활이 무엇인가에 대해서는 아직 구체적으로 밝혀지지 않았다. $24,\;25-(OH)_{2}CC$나 $1.25-(OH)_{2}CC$는 모두 공통적으로 또 다른 active form인 $1.24,\;25-(OH)_{3}CC$를 형성할 수도 있다. 그중 $1.25-(OH)_{2}CC$는 Steroid H.으로 일컬어지기도 하는 Vit. D metabolite중에서 가장 활성을 가진 형태이며 표적기관으로 크게 소장, 뼈, 신장을 들 수 있다. 소장에서의 역활은 무엇보다도 Ca흡수에 관련되는 것으로 소장에서의 Ca흡수와 Ca BP합성에 관여한다. 골격 형성과 뼈의 mineralization에 관여하는 Vit. D metabolite를의 효과에 관해서는 아직까지 일관성있는 보고가 없다. 한편 $1.25-(OH)_{2}CC$는 side chain oxidation을 거쳐 $CO_{2}$와 미지의 물질을 생성하는데 이 mechanism이 어떤 의미를 갖는지는 분명치 않다. 그밖에 또 다른 표적기관으로서 최근 타액선의 존재가 알려졌으며 Vit. D가 배설되는 경로에 대해서는 새로운 바가 없다. Vit. D가 담즙을 통해서 우선적으로 배설되고 소량이 뇨를 통해 배설되는데 metabolite들의 배설경로는 더욱 규명되어야 할 과제이다.

• Journal of Food Hygiene and Safety
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• v.18 no.3
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• pp.153-160
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• 2003

This study was performed to determine the urinary metabolites of methidathion in rats. Urine samples were collected for 24 hours in metabolic cages following after oral administration and dermal application of methidation to rats. The urinary metabolites were identified by GC/MS and the excretion time courses of urinary dialkyl phosphate metabolites were analyzed by CG/FPD. The results obtained are summarized as follows: Three dialkyl phosphate metabolites, DMP, DMTP. and DMDTP, were detected in the rat urine. Urinary dialkyl phosphate metabolites were identified on the basis of their mass spectra by GC/MS. The molecular ions of DMP, DMTP,and DMDTP, were identified at m/z 198, and m/z 158, respectively. A comparison of excretion time courses of urinary dialkyl phosphate metabolites between the orally administrated and dermally applicated rats were also established, After oral administration, 79.2% of DMP, 93.9% of DMTP, and 83.0% of DMDTP were excreted into the urine by 12, 24, and 12 hours, respectively. After dermal application, 71.1% of DMP, 82.8% of DMTP 87.7% of DMDTP were excreted into the urine by 24, 48, 48 hours, respectively. Consequently, almost all of the dialkyl phosphates in oral administration were excreted within 48 hours. However, the metabolites in dermal application were excreted up to 168 hours. In the study, three urinary metabolites of methidation, DMP, DMTP and DMDTP, were detected in the rat both after oral administraion and dermal application with methidathion. And the urinary excretion in dermal application was more delayed than that in oral administration. Based on the results, it tis suggested that three urinary dealkyl phosphates, DMP, DMTP, and DMDTP, could be used as the biomarkers of exposure for methidathion.

• Journal of the Korean Applied Science and Technology
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• v.29 no.1
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• pp.71-80
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• 2012

Vinca alkaloids produced from Catharanthus roseus are one of the most important natural product drugs in treatments of human cancers. These anticancer drugs are derived from coupling of the two monomeric indole alkaloids, catharanthine and vindoline. In order to investigate vindoline biosynthesis, tabersonine-$CD_3$ 1a is synthesized to use as a deuterium labeled precursor, which is distinguished clearly from the natural counterpart. We show that these deuterium labeled tabersonine 1a are successfully incorporated into the vindoline biosynthetic pathway to yield three deuterated vindoline intermediates. 16-Hydroxytabersonine-$CD_3$ (m/z 356) 2a, 16-Methoxytabersonine-$CD_3$ (m/z 370) 3a, 16-Methoxy-2,3-dihydro-3-hydroxytabersonine-$CD_3$ (m/z 388) 4a are produced from the cell suspension culture measured by UPLC/MS at 5 and 13 days after feeding tabersonine. The conversion rates from 1a to 2a and 2a to 3a are fast, whereas that from 3a to 4a is much slower. This indicates that the rate determining step among the first three vindoline biosynthesis is the last step. As a result of the slow conversion rate from 3a to 4a, the accumulation level of 16-Methoxytabersonine-$CD_3$ 3a is significantly increased up to 13 days. The accumulation ratio among 2a, 3a and 4a is 1, 2 and 0.1 at 5 days. However, the peaks of desacetoxyvindoline-$CD_3$ 5a, deacetylvindoline-$CD_3$ 6a and vindoline-$CD_3$ 7a are not found from the cell extracts even after 13 days of incubation which may indicate no presence of their corresponding enzymes.

• Journal of Life Science
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• v.30 no.2
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• pp.211-220
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• 2020

The activity of CAR can be regulated not only by ligand binding but also by phosphorylation of regulatory factors involved in extracellular signaling pathways, cross-talk interactions with transcription factors, and the recruitment, degradation, and expression of coactivators and corepressors. This regulation of CAR activity can in turn have effects on the control of diverse physiological homeostasis, including xenobiotic and energy metabolism, cellular proliferation, and apoptosis. CAR is phosphorylated by the ERK1/2 signaling pathway, which causes formation of a complex with Hsp-90 and CCRP, leading to its cytoplasmic retention, whereas phenobarbital inhibits ERK1/2, which causes dephosphorylation of the downstream signaling molecules, leading to the recruitment to CAR of the activated RACK-1/PP2A components for the dephosphorylation, nuclear translocation, and the transcriptional activation of CAR. Activated CAR cross-talks with FoxO1 to induce inhibition of its transcriptional activity and with PGC-1α to induce protein degradation by ubiquitination, resulting in the transcriptional suppression of PEPCK and G6Pase involved in gluconeogenesis. Regulation by CAR of lipid synthesis and oxidation is achieved by its functional cross-talks, respectively, with PPARγ through the degradation of PGC-1α to inhibit expression of the lipogenic genes and with PPARα through either the suppression of CPT-1 expression or the interaction with PGC-1α each to induce tissue-specific inhibition or stimulation of β-oxidation. Whereas CAR stimulates cellular proliferation by suppressing p21 expression through the inhibition of FoxO1 transcriptional activity and inducing cyclin D1 expression, it suppresses apoptosis by inhibiting the activities of MKK7 and JNK-1 through the expression of GADD45B. In conclusion, CAR is involved in the maintenance of homeostasis by regulating not only xenobiotic metabolism but also energy metabolism, cellular proliferation, and apoptosis through diverse cross-talk interactions with extracellular signaling pathways and intracellular regulatory factors.

• Clinical and Experimental Pediatrics
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• v.48 no.4
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• pp.380-386
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• 2005

Purpose : The incidence of nonphysiologic neonatal hyperbilirubinemia is twice as high in East Asians as in whites. Recently, UGT1A1 mutation was found to be a risk factor for neonatal hyperbilirubinemia. In congenitally-jaundiced Gunn rats, which lack expression of UDP-glucuronosyltransferase, alternative pathways can be stimulated by inducers of CYP1A1 and CYP1A2 enzymes. CYP1A2 plays a major role in bilirubin degradation of the alternate pathway. We studied the relationship between UGT1A1 and CYP1A2 gene polymorphism of neonatal hyperbilirubinemia in Koreans. Methods : Seventy-nine Korean full term neonates who had hyperbilirubinemia(serum bilirubin >12 mg/dL) without obvious causes of jaundice, were analyzed for UGT1A1 and CYP1A2 gene polymorphism; the control group was sixty-eight. We detected the polymorphism of Gly71Arg of UGT1A1 gene by direct sequencing and T2698G of CYP1A2 by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) using MboII and direct sequencing. Results : Allele frequency of Gly71Arg mutation in the hyperbilirubinemia group was 32 percent, which was significantly higher than 11 percent in the control group(P<0.0001). Mutant gene frequency of T2698G was 41.8 percent in patients and 32.3 percent in the control group(P=0.015), but allele frequency was 21 percent in patients and 19 percent in the control group, which was not significantly higher(P=0.706). There was no relationship between mutations of two genes(P=0.635). Conclusion : The polymorphism of UGT1A1 gene(Gly71Arg) and CYP1A2 gene(T2698G) was detected in Korean neonatal hyperbilirubinemia. Only polymorphisms of Gly71Arg in UGT1A1 were significantly higher than control group.