You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output.
Click here to find out more.
Mendeley readers
Attention Score in Context
| Title |
Reductive activation of ricin and ricin A-chain immunotoxins by protein disulfide isomerase and thioredoxin reductase
|
|---|---|
| Published in |
Biochemical Pharmacology, May 2004
|
| DOI | 10.1016/j.bcp.2004.01.013 |
| Pubmed ID | |
| Authors |
Giuseppe Bellisola, Giulio Fracasso, Rodolfo Ippoliti, Gianfranco Menestrina, Anders Rosén, Silvia Soldà, Silvia Udali, Rossella Tomazzolli, Giuseppe Tridente, Marco Colombatti |
| Abstract |
Intracellular activation of ricin and of the ricin A-chain (RTA) immunotoxins requires reduction of their intersubunit disulfide(s). This crucial event is likely to be catalyzed by disulfide oxidoreductases and precedes dislocation of the toxic subunit to the cytosol. We investigated the role of protein disulfide isomerase (EC 5.3.4.1, PDI), thioredoxin (Trx), and thioredoxin reductase (EC 1.8.1.9, TrxR) in the reduction of ricin and of a ricin A-chain immunotoxin by combining enzymatic assays, SDS-PAGE separation and immunoblotting. We found that, whereas PDI, Trx, and TrxR used separately were unable to directly reduce ricin and the immunotoxin, PDI and Trx in the presence of TrxR and NADPH could reduce both ricin and immunotoxin in vitro. PDI functioned only after pre-incubation with TrxR and the reductive activation of ricin was more efficient in the presence of glutathione. Similar results were obtained with microsomal membranes or crude cell extracts. Pre-incubation with the gold(I) compound auranofin, which irreversibly inactivates TrxR, resulted in a dose-dependent inhibition of ricin and immunotoxin reduction. Reductive activation of ricin and immunotoxin decreased or was abolished in microsomes depleted of TrxR and in cell extracts depleted of both PDI and Trx. Pre-incubation of U-937, Molt-3, Jurkat, and DU145 cells with auranofin significantly decreased ricin cytotoxicity with respect to mock-treated controls (P<0.05). Conversely, auranofin failed to protect cells from the toxicity of pre-reduced ricin which does not require intracellular reduction of disulfide between the two ricin subunits. We conclude that TrxR, by activating disulfide reductase activity of PDI, can ultimately lead to reduction/activation of ricin and immunotoxin in the cell. |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 3% |
| Unknown | 37 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 13 | 34% |
| Student > Bachelor | 7 | 18% |
| Professor | 4 | 11% |
| Student > Ph. D. Student | 2 | 5% |
| Student > Master | 2 | 5% |
| Other | 5 | 13% |
| Unknown | 5 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 13 | 34% |
| Biochemistry, Genetics and Molecular Biology | 10 | 26% |
| Immunology and Microbiology | 3 | 8% |
| Neuroscience | 2 | 5% |
| Unspecified | 1 | 3% |
| Other | 3 | 8% |
| Unknown | 6 | 16% |
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 05 January 2024.
All research outputs
#8,534,976
of 25,374,647 outputs
Outputs from Biochemical Pharmacology
#2,521
of 7,685 outputs
Outputs of similar age
#20,974
of 62,294 outputs
Outputs of similar age from Biochemical Pharmacology
#15
of 36 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,685 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one is in the 21st percentile – i.e., 21% 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 62,294 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.