Inter-Laboratory Variability in the Madin-Darby Canine Kidney Cell ProteomeInter-Laboratory Variability in the Madin-Darby Canine Kidney Cell Proteome
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ABSTRACT: Madin-Darby Canine Kidney (MDCK) cells are widely used to study epithelial cell functionality. Their low endogenous drug transporter protein levels make them an amenable system to investigate trans-epithelial permeation and drug transporter protein activity after their transfection. MDCK cells display diverse phenotypic traits and as such laboratory-to-laboratory variability in drug permeability assessments are observed. Consequently, In Vitro-In Vivo extrapolation (IVIVE) approaches using permeability and/or transporter activity data require calibration. A comprehensive proteomic quantification of eleven filter-grown parental or mock-transfected MDCK monolayers from eight different pharmaceutical laboratories using the Total Protein Approach (TPA) is provided. TPA enabled estimations of key morphometric parameters such as monolayer cellularity and volume. Overall, metabolic liability to xenobiotics is likely to be limited for MDCK cell due to the low expression of required enzymes. SLC16A1 (MCT1) was the highest abundance SLC transporter linked to xenobiotic activity, while ABCC4 (MRP4) was the highest abundant ABC transporter. Our data supports existing findings that Claudin-2 levels may be linked to tight junction modulation, thus impacting trans-epithelial resistance. This unique database provides data on more than 8000 proteins copy number and concentrations, thus allowing an in-depth appraisal of the control monolayers used in each laboratory.
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Zea Mays (maize)
TISSUE(S): Liver
SUBMITTER: Jacek Wisniewski
LAB HEAD: Jacek R Wisniewski
PROVIDER: PXD039552 | Pride | 2023-07-20
REPOSITORIES: Pride
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