Regulation of Arsenic Triglutathione [As(GS) <sub>3</sub> ] Transport by the Human Multidrug Resistance Protein 1 (MRP1/ABCC1) Through Post‐translational Modification
Bibliographic record
Abstract
The 190‐kDa ATP‐binding cassette transporter, MRP1, is responsible for exporting a diverse array of substrates from the cell including glutathione conjugates. Arsenic, a high priority environmental carcinogen and clinical anti‐cancer agent, is a substrate of MRP1 in its trigluathione form [As(GS) 3 ]. We initially characterized As(GS) 3 transport by MRP1 using membrane vesicles isolated from a doxorubicin‐selected small cell lung cancer cell line (H69AR) and found it to be a high apparent affinity substrate (K m 0.3 μM). In the current study, we show that the K m of MRP1 for As(GS) 3 depends upon the cell line it is expressed in. Thus, wild‐type MRP1‐enriched membrane vesicles exhibit a >10‐fold difference in K m for As(GS) 3 (0.3 μM vs 4.4 μM) when prepared from transfected HeLa vs HEK293 cells, respectively. On the other hand, mutant MRP1 lacking all N‐linked glycosylation (sugar‐free) expressed in either cell line exhibits a low K m (0.3 – 0.6 μM). Furthermore, when prepared in the presence of phosphatase inhibitors, both wild‐type and sugar‐free MRP1‐enriched membrane vesicles from either HeLa or HEK293 cells exhibit a high K m for As(GS) 3 (3 – 6 μM). Together, these results suggest that the affinity of MRP1 for As(GS) 3 is influenced by cell type, phosphorylation, and glycosylation and elucidate potential implications for the relative detoxification of arsenic by different cell types and tissues.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".