Eur J Endocrinol
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

DOI: 10.1530/eje.1.01813
European Journal of Endocrinology, Vol 152, Issue 1, 119-125
Copyright © 2005 by European Society of Endocrinology
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vendrame, F.
Right arrow Articles by Dotta, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vendrame, F.
Right arrow Articles by Dotta, F.
CLINICAL STUDY

Defective lymphocyte caspase-3 expression in type 1 diabetes mellitus

Francesco Vendrame, Carmela Santangelo1, Roberta Misasi2, Sabrina Dionisi, Chiara Gizzi2, Massimo Realacci2, Daniele Grassetti3, Umberto Di Mario and Francesco Dotta3

Department of Clinical Sciences-Endocrinology, University ‘La Sapienza’, Rome, Italy, 1 National Center for Food Quality and Risk Assessment, Istituto ‘Superiore di Sanita’, Rome, Italy, 2 Department of Experimental Medicine and Pathology, University ‘La Sapienza’, Rome, Italy and 3 Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy

(Correspondence should be addressed to F Dotta, U. O. di Diabetologia, 3° Lotto, 5S, Policlinico ‘Le Scotte’, Viale Bracci 18, 53100 Siena, Italy; Email: fradotta{at}tin.it)

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.




This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
F. Vendrame, M. Segni, D. Grassetti, V. Tellone, G. Augello, V. Trischitta, M. Torlontano, and F. Dotta
Impaired Caspase-3 Expression by Peripheral T Cells in Chronic Autoimmune Thyroiditis and in Autoimmune Polyendocrine Syndrome-2
J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5064 - 5068.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 European Society of Endocrinology.