• Title/Summary/Keyword: p-gp

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Exocyclic GpC DNA methyltransferase from Celeribacter marinus IMCC12053 (Celeribacter marinus IMCC12053의 외향고리 GpC DNA 메틸트랜스퍼라아제)

  • Kim, Junghee;Oh, Hyun-Myung
    • Korean Journal of Microbiology
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    • v.55 no.2
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    • pp.103-111
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    • 2019
  • DNA methylation is involved in diverse processes in bacteria, including maintenance of genome integrity and regulation of gene expression. CcrM, the DNA methyltransferase conserved in Alphaproteobacterial species, carries out $N^6$-adenine or $N^4$-cytosine methyltransferase activities using S-adenosyl methionine as a co-substrate. Celeribacter marinus IMCC12053 from the Alphaproteobacterial group was isolated from a marine environment. Single molecule real-time sequencing method (SMRT) was used to detect the methylation patterns of C. marinus IMCC12053. Gibbs motif sampler program was used to observe the conversion of adenosine of 5'-GANTC-3' to $N^6$-methyladenosine and conversion of $N^4$-cytosine of 5'-GpC-3' to $N^4$-methylcytosine. Exocyclic DNA methyltransferase from the genome of strain IMCC12053 was chosen using phylogenetic analysis and $N^4$-cytosine methyltransferase was cloned. IPTG inducer was used to confirm the methylation activity of DNA methylase, and cloned into a pQE30 vector using dam-/dcm- E. coli as the expression host. The genomic DNA and the plasmid carrying methylase-encoding sequences were extracted and cleaved with restriction enzymes that were sensitive to methylation, to confirm the methylation activity. These methylases protected the restriction enzyme site once IPTG-induced methylases methylated the chromosome and plasmid, harboring the DNA methylase. In this study, cloned exocyclic DNA methylases were investigated for potential use as a novel type of GpC methylase for molecular biology and epigenetics.

Gypenoside XVII protects against myocardial ischemia and reperfusion injury by inhibiting ER stress-induced mitochondrial injury

  • Yu, Yingli;Wang, Min;Chen, Rongchang;Sun, Xiao;Sun, Guibo;Sun, Xiaobo
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.642-653
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    • 2021
  • Background: Effective strategies are dramatically needed to prevent and improve the recovery from myocardial ischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum (ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotective effects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury, and their crosstalk within I/R injury and in GP-17einduced cardioprotection are also explored. Methods: Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects of GP-17 on mitochondrial function including mitochondrial permeability transition pore opening, reactive oxygen species production, and respiratory function were determined using fluorescence detection kits on mitochondria isolated from the rat hearts. H9c2 cardiomyocytes were used to explore the effects of GP-17 on hypoxia/reoxygenation. Results: We found that GP-17 inhibits myocardial apoptosis, reduces cardiac dysfunction, and improves contractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantly mediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotective effects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways. Conclusion: GP-17 inhibits I/R-induced mitochondrial injury by delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.

Effect of Drugs on the Cardiac Transport, Metabolism and Action of Idarubicin: Pharmacokinetic and Pharmacodynamic Modeling

  • Kang, Won-Ku
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.212-213
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    • 2002
  • Using the isolated perfused rat heart this study investigated 1) the cardiac uptake of idarubicin (IDA), 2) the role of P-glycoprotein (P-gp) in the uptake process, 3) the formation of IDOL from IDA in the heart, and 4) the effect of P-gp inhibitors (verapamil, amiodarone, PSC 833), doxorubicin, hypothermia, xanthine derivatives (caffeine, theophylline) and metabolism inhibitors (rutin, phenobarbital) on the pharmacokinetics and pharmacodynamics of IDA using a mathematical modeling approach. A minimal model was constructed; the differential equations were numerically solved and fitted to the data using the ADAPT II-software package using maximum likelihood estimation assuming that the measurement error has a standard deviation which is a linear function of the measured quantity[1]. (omitted)

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Evaluation of antimicrobial activity and efficacy of herbal oils and extracts in disinfection of gutta percha cones before obturation

  • Makade, Chetana S.;Shenoi, Pratima R.;Morey, Elakshi;Paralikar, Ameya V.
    • Restorative Dentistry and Endodontics
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    • v.42 no.4
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    • pp.264-272
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    • 2017
  • Objectives: Literature has shown that micro-organisms contaminate gutta percha (GP) during storage and manipulation. Till date herbal extracts are not explored as an alternative medicament for pre-operative chairside disinfection of GP cones. The purpose of our study was to evaluate the antimicrobial activity and efficacy of lemon grass oil (LG), basil oil (BO), and obicure tea extract (OT) in disinfecting GP cones before obturation. Materials and Methods: Agar diffusion method was used to evaluate the antimicrobial efficacy of LG, BO, OT, and sodium hypochlorite (control) against common contaminants, namely, Enterococcus faecalis, Staphylococcus aureus, and Candida albicans. One hundred and twenty GP cones were contaminated and cut into 2. First half was placed in the broth and incubated; whereas the second was treated with herbal extracts for 1 minute and then incubated for 24 hours in the broth. Any inhibition in bacterial growth was noted with presence/absence of turbidity. Two-way analysis of variance and ${\chi}^2$ test were used to assess the effectiveness of herbal extracts to decontaminate GP. Results: LG showed the highest inhibition zones ($29.9{\pm}6.9mm$) for all tested organisms, followed by OT extract ($16.3{\pm}1.8mm$), sodium hypochlorite ($16.0{\pm}1.6mm$), and BO ($14.5{\pm}5.3mm$). Statistically significant difference was observed between LG and other herbal extracts (p < 0.05). Conclusions: All extracts proved to be potential rapid chairside disinfectants of GP cones with LG showing the highest antimicrobial activity.

Study on Water quality and Release Rate of Sediment in Gul-po Stream (굴포천 유역의 수질 및 퇴적물 용출 특성에 관한 연구)

  • Jung, Jae-Hoon;Ahn, Tae-Woong;Choi, I-Song;Oh, Jong-Min
    • Proceedings of the Korea Water Resources Association Conference
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    • 2010.05a
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    • pp.966-970
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    • 2010
  • 본 연구의 대상지인 인천광역시, 부천시, 서울특별시, 김포시를 걸쳐서 흐르는 굴포천은 산업화와 도시화로 인한 생활하수 및 공장폐수의 유입, 느린 유속과 하천 복개 등과 같은 유입오염원과 하천 구조적 문제로 인하여 수질이 악화되어 왔다. 특히 하천변의 소규모 영세 공장, 중 상류에 형성된 대규모 공업단지, 지역개발에 따른 인구증가로 인한 생활하수 등은 굴포천의 주 오염원이다. 또한 직강화된 하도와 느린 유속 등 하천의 구조적인 문제점 등은 하천의 자정능력을 저하시키고 있어 현재 굴포천의 수질수준은 전국 최하위에 머물러 있다. 더욱이 입자상 오염물질의 퇴적으로 인하여 굴포천의 하상은 대부분 퇴적오니가 형성되어 있다. 이러한 퇴적오니는 다량의 유기 물질 및 중금속 등을 흡착하고 있고, 재용출에 의한 내부오염 가능성을 내포하고 있기 때문에 오염원이 제거된 후에도 계속적인 수질오염을 일으킬 수 있다(Alloway et al, 1988). 따라서 본 연구에서는 굴포천 본류 전 구간 및 유입지천에 대하여 수질 오염도와 오염부하량을 산정하였으며, 본류 하상 퇴적물의 오염도 및 퇴적물의 용출특성에 관한 조사를 수행하였다. 본 연구는 굴포천 본류 구간을 최상류(GP-1)부터 최하류(GP-7)구간까지 총 7개 구간으로 구분하여 실시하였으며 각 지점별 수질 및 퇴적물 오염도를 조사하였다. 또한 3개의 유입지천에 대하여 수질 오염도 및 오염부하량을 산정하였다. 굴포천 하상의 경우 최상류의 GP-1지점을 제외하고는 전 구간이 대부분 오염된 오니가 퇴적되어 있으며, 이러한 퇴적오니의 퇴적물 오염도를 분석해본 결과 상류부인 GP-1, GP-2와 유속이 비교적 빠른 GP-7지점에 비하여 나머지 지점들의 오염도가 매우 높은 것으로 나타났다. 이러한 하상퇴적물의 영양염류 용출특성을 알아보기 위하여 호기 및 혐기조건에서 용출실험을 실시한 결과 호기와 혐기 조건에서 T-N은 각각 34.84 $mg/m^2/day$, 66.93 $mg/m^2/day$의 용출속도를 보였고, T-P의 경우 호기 조건 시 5.33 $mg/m^2/day$, 혐기 조건 시 6.84 $mg/m^2/day$의 용출속도를 보임으로서 퇴적물 용출에 의한 내부오염의 가능성이 있음을 보였다.

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Expression and Characterization of Human T-Cell Leukemia Virus Type-I Env and Gag Proteins

  • Son, Kyung-Hwa;Kim, Byong-Moon;Lee, Taik-You;Kim, Seong-Ryong;Kim, Kun-Soo;Lee, Jeong-Kug;Yang, Jai-Myung
    • Journal of Microbiology and Biotechnology
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    • v.9 no.3
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    • pp.311-317
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    • 1999
  • Human T-cell leukemia virus Type-I (HTLV-I) is etiologically associated with rare adult T-cell leukemia, a malignant T-cell disorder. cDNAs encoding p24 (gag), gp21(env), and pXII of HTLV-I were amplified by polymerase chain reaction (PCR) using the genomic DNA extracted from HUT102 cell line as a template. The amplified cDNAs were cloned into the Escherichia coli expression vectors and over-expression of the recombinant proteins were achieved by adding IPTG into the culture media in order to induce the promoter. The molecular weights of the recombinant p24, gp21, and pXII, determined by SDS-PAGE, were found to be approximately 28 kDa, 23 kDa, and 15 kDa, respectively. Reactivity of the recombinant proteins with human sera was tested by the immunoblot assay. The gp21 and p24 reacted against the sera obtained from HTLV-I-infected individuals but not against the sera obtained from normal persons. These results suggest that the recombinant proteins expressed in E. coli were recognized by antibodies in sera from HTLV-I infected patients. These recombinant proteins would be applicable for detecting the presence of antibodies against HTLV-I in human blood samples.

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Mechanism of Intestinal Transport of an Organic Cation, Tributylmethylammonium in Caco-2 Cell Monolayers

  • Hong Soon-Sun;Moon Sang-Cherl;Shim Chang-Koo
    • Archives of Pharmacal Research
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    • v.29 no.4
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    • pp.318-322
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    • 2006
  • Many quaternary ammonium salts are incompletely absorbed after their oral administration and may also be actively secreted into the intestine. However, the underlying mechanism(s) that control the transport of these cations across the intestinal epithelium is not well understood. In this study, the mechanism of absorption of quaternary ammonium salts was investigated using Caco-2 cell monolayers, a human colon carcinoma cell line. Tributylmethylammonium (TBuMA) was used as a model quaternary ammonium salts. When TBuMA was administrated at a dose of 13.3 imole/kg via iv and oral routes, the AUC values were $783.7{\pm}43.6\;and\;249.1{\pm}28.0{\mu}mole\;min/L$ for iv and oral administration, indicating a lower oral bioavailability of TBuMA $(35.6\%)$. The apparent permeability across Caco-2 monolayers from the basal to the apical side was 1.3 times (p<0.05) greater than that from the apical to the basal side, indicating a net secretion of TBuMA in the intestine. This secretion appeared to be responsible for the low oral bioavailability of the compound, probably mediated by p-gp (p-glycoprotein) located in the apical membrane. In addition, the uptake of TBuMA by the apical membrane showed a $Na^+$ dependency. Thus, TBuMA appears to absorbed via a $Na^+$ dependent carrier and is then secreted via p-gp related carriers.

Antimutagenic Effects of Juices from the Peppers in Salmonella Assay System

  • Park, Kun-Young;Kweon, Young-Mi;Rhee, Sook-Hee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.24 no.3
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    • pp.440-445
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    • 1995
  • The antimutagenic effects of juices from green pepper(GP), red pepper leaf(RPL), red pepper(RP) and sweet pepper(SP) were examined by the Ames method using Salmonella typhimurium TA100. The juice supernatants of GP, RPL and RP showed antimutagenic activities against afltoxin B1(AFB1) in Salmonella typhimurium TA 100. The juice supermatants of GP and RPL also exhibited the inhibitory effects(p<0.05) to the mutagenicities induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and 4-nitro-quinoline-1-oxide(4-NQO). The juice of RP showed antimutagenic activities against indirect mutagen of AFB1, however, the activity was reduced at higher concentration(5.0%), furthermore, as the adding concentration of sample increased to 5.0%, it exhibited slight comutagenicith on direct mutagen of MNNG. Theantimutagenic activities of GP and RPL juices were reduced significantly after heating at 100℃ for 20min, supposing that the antimutagenic compound(s) in the juices were heat labile.

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Comparison of predicted adult heights measured by Bayley-Pinneau and Tanner-Whitehouse 3 methods in normal children, those with precocious puberty and with constitutional growth delay (정상 소아, 성조숙증 및 체질성 성장지연 소아에서 Bayley-Pinneau방법과 Tanner-Whitehouse 3방법에 의한 예측성인신장 비교)

  • Oh, Yeon Joung;Yu, Byung Keun;Shin, Jung Yeon;Lee, Kee-Hyoung;Park, Sang Hee;Lee, Kwang Chul;Son, Chang Sung
    • Clinical and Experimental Pediatrics
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    • v.52 no.3
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    • pp.351-355
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    • 2009
  • Purpose : This study compared bone ages measured by the Greulich-Pyle (GP) and Tanner-Whitehouse 3 (TW3) methods and investigated the differences in predicted adult heights measured by Bayley-Pinneau (BP) and TW3 methods. Methods : Bone ages were assessed from left-wrist radiographs by two investigators, one for each GP and TW3 methods in 85 normal children, 30 precocious puberty girls, and 30 constitutional growth delay boys. The differences between the measured predicted adult heights using the BP and TW3 methods were compared in each group. Results : The bone age measured by the TW3 method was less than that by the GP method in normal children. The predicted adult heights measured by the two methods showed no significant difference in normal boys, while the predicted adult height measured by the TW3 method was higher than that by the BP method for normal girls ($156.4{\pm}4.7$ cm vs. $158.9{\pm}3.8$ cm, P<0.01) and for precocious puberty girls ($156.3{\pm}4.0$ cm vs. $159.3{\pm}4.2$ cm, P<0.01). In contrast, the predicted adult height was higher from the BP method than from the TW3 method in constitutional growth delay boys ($173.3{\pm}4.4$ cm vs. $169.7{\pm}3.2$ cm, P<0.01). Conclusion : There were significant differences in predicted adult heights between the BP and TW3 method in normal girls, precocious puberty girls, or constitutional growth delay boys. In precocious puberty and constitutional growth delay, the BP method might be preferred to predict adult height, but further studies on final adult height are needed.

Effects of Naringin on the Bioavailability of Etoposide in Rats

  • Choi, Byung-Chul;Choi, Jun-Shik
    • Journal of Pharmaceutical Investigation
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    • v.38 no.5
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    • pp.313-317
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    • 2008
  • This study investigated the effect of naringin, a flavonoid, on the bioavailability of etoposide administered orally to rats. Etoposide (6 mg/kg) was administered orally to rats alone or with naringin (1, 4 or 12 mg/kg). Compared with the control group, the co-administration of etoposide with 4 and 12 mg/kg of naringin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) and the peak plasma concentration ($C_{max}$) of the oral etoposide. Consequently, the absolute bioavailability (AB) of etoposide in the presence (4 and 12 mg/kg) of naringin was significantly (p<0.05) increased by $9.4{\sim}10.6%$ compared with the control group (7.4%). The relative bioavailability (RB) of etoposide was increased 1.13- to 1.44-fold compared to the control group. Enhanced bioavailability of etoposide might be due to inhibition of both cytochrome P450 (CYP) 3A4 in the intestine or liver and P-glycoprotein (P-gp) transport efflux of etoposide in the intestinal membrane. This data indicate that careful consideration of the dosage for therapy with etoposide is required in a case of clinical application of the co-administration of etoposide and naringin.