| Title: |
Defective lymphocyte caspase-3 expression in type 1 diabetes mellitus. |
| Authors: |
Vendrame F.; Santangelo C.; Misasi R.; Dionisi S.; Gizzi C.; Realacci M.; Grassetti D.; Di Mario U.; DOTTA, FRANCESCO |
| Contributors: |
Vendrame, F.; Santangelo, C.; Misasi, R.; Dionisi, S.; Gizzi, C.; Realacci, M.; Grassetti, D.; Di Mario, U.; Dotta, Francesco |
| Publication Year: |
2005 |
| Collection: |
Università degli Studi di Siena: USiena air |
| Description: |
OBJECTIVE: Activation-induced cell death (AICD) is a major mechanism in the regulation of peripheral tolerance and its impairment can determine the development of autoimmunity. In the present study, in order to evaluate the role of caspase-3 in type 1 diabetes mellitus (T1DM) AICD, caspase-3 expression was analyzed in peripheral blood lymphocytes from 37 new onset T1DM patients and from 36 normal control subjects (NC) in resting conditions and after anti-Fas-triggered apoptosis. METHODS: Caspase-3 expression was determined by semiquantitative RT-PCR and Western blot. Apoptosis was induced in activated lymphocytes by anti-Fas monoclonal antibody and quantified by flow cytometry and morphological analysis. RESULTS: Caspase-3 mRNA expression was reduced in resting lymphocytes in 18/37 T1DM patients and in 1/36 NC (P < 0.01). Patients studied for both Fas-mediated AICD and caspase-3 mRNA expression revealed that a reduced caspase-3 mRNA expression in resting lymphocytes occurred in all patients showing resistance to Fas-mediated apoptosis (T1DM vs NC, P < 0.02) with the exception of 3 patients who exhibited normal caspase-3 expression levels. Caspase-3 protein analysis confirmed mRNA data and showed an impaired expression of caspase-3 active form in T1DM subjects compared with NC. CONCLUSIONS: Our data show that defective expression and function of caspase-3 in peripheral lymphocytes of T1DM patients may contribute to the development of AICD resistance in type 1 diabetes. |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/15762195; info:eu-repo/semantics/altIdentifier/wos/WOS:000226515900014; volume:152; issue:1; firstpage:119; lastpage:125; numberofpages:7; journal:EUROPEAN JOURNAL OF ENDOCRINOLOGY; http://hdl.handle.net/11365/33976 |
| DOI: |
10.1530/eje.1.01813 |
| Availability: |
http://hdl.handle.net/11365/33976; https://doi.org/10.1530/eje.1.01813 |
| Rights: |
info:eu-repo/semantics/closedAccess |
| Accession Number: |
edsbas.FCF9B077 |
| Database: |
BASE |