| Title |
NGF-withdrawal induces apoptosis in pancreatic beta cells in vitro
|
|---|---|
| Published in |
Diabetologia, October 2001
|
| DOI | 10.1007/s001250100650 |
| Pubmed ID | |
| Authors |
D. Pierucci, S. Cicconi, P. Bonini, F. Ferrelli, D. Pastore, C. Matteucci, L. Marselli, P. Marchetti, F. Ris, P. Halban, J. Oberholzer, M. Federici, F. Cozzolino, R. Lauro, P. Borboni, L. N. J. L. Marlier |
| Abstract |
Using primary cultures of human pancreatic islets, purified human pancreatic beta cells and the mouse beta TC6-F7 cell line, we analysed the expression of nerve growth factor, (NGF/NGF) receptors in beta cells. To investigate whether NGF could sub-serve an autocrine antiapoptotic role in beta cells, we studied the effects of NGF withdrawal using a neutralizing monoclonal anti-NGF antibody. The expression of NGF and NGF receptors (gp140(Trk-A) and p75(NTR)) were analysed by RT-PCR and immunofluorescence. Pulse-chase experiments and beta cell/PC12 co-cultures were used to investigate NGF production and secretion from beta cells. Possible apoptosis induced by NGF withdrawal was monitored by phosphatidylserine translocation, nucleosomal formation, DNA laddering and FACS analysis. Involvement of transcription/translation mechanisms were investigated as well as the gp140(Trk-A) required. Finally, signal transduction pathways typically involved in apoptotic mechanisms were analysed by western blot analysis. We show that NGF and both NGF receptors, gp140(Trk-A) and p75(NTR) are expressed in beta cells where NGF is produced and secreted in a biologically active form. NGF-withdrawal induces beta-cell transcription/translation independent apoptosis but mediated by gp140(Trk-A). Analysis of signal transduction pathways revealed that NGF withdrawal inhibits the PI3-K, protein kinase B (AKT), Bad survival pathway and activates c-Jun kinase (JNK) whereas ERKs and p38 mitogen-activated protein kinase (MAPK) are not affected. Moreover, Bcl-XL, but not Bcl-2 protein expression are reduced. We suggest that the integrity of the NGF/NGF receptor system and NGF bioavailability participate in controlling beta-cell survival in culture which represents a key issue for improving possibilities for transplantations in the treatment of diabetes. |
Mendeley readers
The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 44 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 16% |
| Student > Master | 6 | 14% |
| Student > Ph. D. Student | 6 | 14% |
| Student > Bachelor | 5 | 11% |
| Professor > Associate Professor | 4 | 9% |
| Other | 8 | 18% |
| Unknown | 8 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 10 | 23% |
| Medicine and Dentistry | 9 | 20% |
| Neuroscience | 6 | 14% |
| Biochemistry, Genetics and Molecular Biology | 5 | 11% |
| Psychology | 1 | 2% |
| Other | 3 | 7% |
| Unknown | 10 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. 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 28 January 2023.
All research outputs
#4,806,354
of 23,213,531 outputs
Outputs from Diabetologia
#2,046
of 5,107 outputs
Outputs of similar age
#6,775
of 42,730 outputs
Outputs of similar age from Diabetologia
#8
of 29 outputs
Altmetric has tracked 23,213,531 research outputs across all sources so far. Compared to these this one has done well and is in the 76th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,107 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.9. This one has gotten more attention than average, scoring higher than 53% of its peers.
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 42,730 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.