Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In daunorubicin resistant Ehrlich ascites tumor cells (DNR), the initial taurine uptake was reduced by 56% as compared to the parental, drug sensitive Ehrlich cells. Kinetic experiments indicated that taurine uptake in Ehrlich cells occurs via both high- and low-affinity transporters. The maximal rate constant for the initial taurine uptake was reduced by 45% (high-affinity system) and 49% (low affinity system) in the resistant subline whereas the affinity of the transporters to taurine was unchanged. By immunoblotting we identified 3 TauT protein bands in the 50-70 kDa region. A visible reduction in the intensity of the band with the lowest molecular weight was observed in resistant cells. Quantitative RT-PCR indicated a significant reduction in the amount of taurine transporter mRNA in the resistant cells. Drug resistance in DNR Ehrlich cells is associated with overexpression of the mdr1 gene product P-glycoprotein (P-gp). Using 5 progressively DNR resistant Ehrlich cell sublines with different P-gp expression pattern no correlation between taurine uptake and P-gp expression was found. Taurine uptake in MDR1 transfected NIH/3T3 mouse fibroblasts was in contrast to the findings in Ehrlich cells increased compared to the parental fibroblasts. It is concluded that the reduced taurine uptake in resistant Ehrlich cells reflects a down regulation of the taurine transporter at the mRNA and protein level and it is most probably not related to P-gp overexpression.
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PMID:Downregulation of taurine uptake in multidrug resistant Ehrlich ascites tumor cells. 1210 61

Syncytiotrophoblasts play an essential role in restriction of drug delivery through the blood-placenta barrier (BPB). Conditionally immortalized syncytiotrophoblast cell lines, TR-TBTs, were established at gestational day 18 from pregnant transgenic rats (Tg-rats) harboring the temperature-sensitive SV 40 (ts SV40) large T-antigen. TR-TBTs exhibit temperature-sensitive cell growth due to the expression of SV 40 large T-antigen, and thus the cell growth can be regulated by changing the culture temperature. TR-TBTs exhibit typical properties of syncytiotrophoblast cells, such as syncytium-like morphology, the expression of cytokeratins and hormones, and polarized expression of glucose transporter 1 (GLUT1) and GLUT3. TR-TBTs express in vivo influx and efflux transporters, such as taurine transporter (TauT), betaine/GABA transporter (BGT-1), amino acid transporter 2 (ATA2), organic anion transporting polypeptide 2 (oatp2), organic cation/carnitine transporter (OCTN2), P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP/ABCG2). Moreover, TR-TBTs exhibit taurine, GABA, and DHEA-S uptake activity via TauT, BGT-1, and oatp2, respectively. Therefore, TR-TBTs can be used for the analysis of these functions and would be a good in vitro models for investigating carrier-mediated transport functions at the BPB.
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PMID:Conditionally immortalized syncytiotrophoblast cell lines as new tools for study of the blood-placenta barrier. 1518 10