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Mendeley readers
Attention Score in Context
| Title |
Cystine-Glutamate Transporter SLC7A11 Mediates Resistance to Geldanamycin but Not to 17-(Allylamino)-17-demethoxygeldanamycin
|
|---|---|
| Published in |
Molecular Pharmacology, September 2007
|
| DOI | 10.1124/mol.107.039644 |
| Pubmed ID | |
| Authors |
Ruqing Liu, Paul E Blower, Anh-Nhan Pham, Jialong Fang, Zunyan Dai, Carolyn Wise, Bridgette Green, Candee H Teitel, Baitang Ning, Wenhua Ling, Beverly D Lyn-Cook, Fred F Kadlubar, Wolfgang Sadée, Ying Huang |
| Abstract |
The cystine-glutamate transporter SLC7A11 has been implicated in chemoresistance, by supplying cystine to the cell for glutathione maintenance. In the NCI-60 cell panel, SLC7A11 expression shows negative correlation with growth inhibitory potency of geldanamycin but not with its analog 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), which differs in the C-17 substituent in that the the methoxy moiety of geldanamycin is replaced by an amino group. Structure and potency analysis classified 18 geldanamycin analogs into two subgroups, "17-O/H" (C-17 methoxy or unsubstituted) and "17-N" (C-17 amino), showing distinct SLC7A11 correlation. We used three 17-O/H analogs and four 17-N analogs to test the role of the 17-substituents in susceptibility to SLC7A11-mediated resistance. In A549 cells, which are resistant to geldanamycin and strongly express SLC7A11, inhibition of SLC7A11 by (S)-4-carboxyphenylglycine or small interfering RNA increased sensitivity to 17-O/H, but had no effect on 17-N analogs. Ectopic expression of SLC7A11 in HepG2 cells, which are sensitive to geldanamycin and express low SLC7A11, confers resistance to geldanamycin, but not to 17-AAG. Antioxidant N-acetylcysteine, a precursor for glutathione synthesis, completely suppressed cytotoxic effects of 17-O/H but had no effect on 17-N analogs, whereas the prooxidant ascorbic acid had the opposite effect. Compared with 17-AAG, geldanamycin led to significantly more intracellular reactive oxygen species (ROS) production, which was quenched by addition of N-acetylcysteine. We conclude that SLC7A11 confers resistance selectively to 17-O/H (e.g., geldanamycin) but not to 17-N (e.g., 17-AAG) analogs partly as a result of differential dependence on ROS for cytotoxicity. Distinct mechanisms could significantly affect antitumor response and organ toxicity of these compounds in vivo. |
Mendeley readers
The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Switzerland | 1 | 3% |
| Canada | 1 | 3% |
| Denmark | 1 | 3% |
| China | 1 | 3% |
| United States | 1 | 3% |
| Unknown | 31 | 86% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 28% |
| Researcher | 7 | 19% |
| Student > Bachelor | 5 | 14% |
| Student > Master | 4 | 11% |
| Student > Postgraduate | 2 | 6% |
| Other | 4 | 11% |
| Unknown | 4 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 16 | 44% |
| Biochemistry, Genetics and Molecular Biology | 7 | 19% |
| Medicine and Dentistry | 4 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Social Sciences | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 6 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 April 2024.
All research outputs
#7,565,251
of 23,075,872 outputs
Outputs from Molecular Pharmacology
#1,108
of 3,294 outputs
Outputs of similar age
#25,295
of 71,476 outputs
Outputs of similar age from Molecular Pharmacology
#16
of 35 outputs
Altmetric has tracked 23,075,872 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,294 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 71,476 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.