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P‐glycoprotein overexpression in MDCKII kidney cells is associated with increased cholesterol efflux to high density lipoprotein

2011· article· en· W3175341947 on OpenAlexaff
Carlos León, Kishor M. Wasan

Bibliographic record

VenueThe FASEB Journal · 2011
Typearticle
Languageen
FieldMedicine
TopicDrug Transport and Resistance Mechanisms
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsEffluxP-glycoproteinCholesterolHMG-CoA reductaseKidneyABCA1ReductaseHigh-density lipoproteinApolipoprotein BLipoproteinChemistryBiologyEndocrinologyInternal medicinePharmacologyBiochemistryEnzymeTransporterMedicineGeneMultiple drug resistance

Abstract

fetched live from OpenAlex

We investigated the role of P-glycoprotein (Pgp) in cholesterol metabolism in canine kidney (MDCKII) cells which overexpressed Pgp (MDCKII-MDR1). Pgp overexpression was confirmed by immunoblotting and by daunorubicin uptake studies. MDCKII-MDR1 kidney cells showed a three-fold increase in HMG CoA reductase expression with no changes in cholesterol cellular levels compared to MDCKII controls. Furthermore, cholesterol synthesis was significantly increased by 30% in MDCKII-MDR1 cells compared to MDCKII controls consistent with the increase in HMG CoA reductase expression. Cholesterol efflux to HDL was significantly increased by 40% in Pgp overexpressing cells compared to controls. This effect was specific as cholesterol efflux to Apolipoprotein A1 was not affected by the Pgp overexpression in these cells. High density lipoprotein (HDL) uptake was not affected by Pgp overexpression in MDCKII cells. These findings suggest that Pgp contributes to cholesterol efflux to HDL in kidney cells. The subcellular localization of Pgp in kidney cells and the fact that cholesterol has been found in urine from patients with nephropathies, suggest that Pgp may modulate cholesterol efflux to HDL in these clinical conditions.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.014
GPT teacher head0.210
Teacher spread0.196 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2011
Admission routes1
Has abstractyes

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