Document Detail


Expression ratios of the Bcl-2 family proteins and disease activity in multiple sclerosis.
MedLine Citation:
PMID:  12507784     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is emerging evidence that failure of apoptosis (programmed cell death) of potentially pathogenic T lymphocytes may be involved in the pathogenesis of multiple sclerosis (MS). The commitment of T lymphocytes to die is partly regulated by the Bcl-2 family proteins, which act as a checkpoint upstream of mitochondrial dysfunction. These proteins include the death antagonists Bcl-2 and Bcl-X(L), and death agonists Bax and Bad. Recent studies suggest that altered expression of Bcl-2 family proteins in T lymphocytes is involved in promoting cellular resistance to apoptosis in patients with MS. However, the relationship between these alterations in Bcl-2 proteins expression and clinical disease activity has not yet been evaluated. In this study, we analyzed the expression ratios of pro- to anti-apoptosis Bcl-2 family proteins in patients with clinically active MS and compared results to corresponding ratios in patients with stable MS and relevant control groups. We observed a significant reduction in the expression ratios of pro- to anti-apoptosis Bcl-2 members in peripheral lymphocytes from patients with active MS when compared to corresponding ratios in patients with stable MS or other controls. This imbalance in the expression ratios of pro- and anti-apoptosis proteins was functionally active in reducing cellular susceptibility to apoptosis in active MS. It also correlated with clinical features of disease activity, such as the number of gadolinium-enhancing MRI lesions and clinical relapses. Our findings indicate that dysregulated expression of Bcl-2 family proteins in peripheral lymphocytes is a feature of clinically active multiple sclerosis.
Authors:
M K Sharief; H Matthews; M A Noori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroimmunology     Volume:  134     ISSN:  0165-5728     ISO Abbreviation:  J. Neuroimmunol.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2002-12-31     Completed Date:  2003-02-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8109498     Medline TA:  J Neuroimmunol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  158-65     Citation Subset:  IM    
Affiliation:
Department of Neuroimmunology, Guy's, King's and St. Thomas' School of Medicine, Guy's Hospital, London SE1 1UL, UK. m.k.sharief@kcl.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD95 / blood,  immunology
Apoptosis / genetics,  immunology*
Carrier Proteins / blood,  immunology
Cell Division / immunology
Chemotaxis, Leukocyte / genetics,  immunology*
Cytochrome c Group / blood
Female
Gene Expression Regulation / immunology
Humans
Male
Multiple Sclerosis / blood,  immunology*,  physiopathology
Proto-Oncogene Proteins / blood,  immunology
Proto-Oncogene Proteins c-bcl-2 / blood,  immunology*
Recurrence
T-Lymphocytes / immunology*,  metabolism
bcl-2-Associated X Protein
bcl-Associated Death Protein
bcl-X Protein
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/BAD protein, human; 0/BAX protein, human; 0/BCL2L1 protein, human; 0/Carrier Proteins; 0/Cytochrome c Group; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 0/bcl-Associated Death Protein; 0/bcl-X Protein

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