Abstract:
:Apoptotic deletion of autoreactive T-cells is defective in patients with multiple sclerosis (MS). Glatiramer acetate (GA) treatment seems to restore apoptosis of detrimental T-cells. We analyzed the mitochondria membrane pro- (Bax) and anti-apoptotic (Bcl- 2) and cytosolic pro-apoptotic (Cyt-c, APAF-1) proteins expression in peripheral lymphocytes from relapsing-remitting (RR) MS patients during GA treatment. Blood samples were collected from 8 healthy controls (HCs) and from 8 RR MS patients prior to and every three months during the 9 months of GA treatment. Peripheral blood mononuclear cells (PBMNCs) Bcl-2, Bax, Cyt-c and APAF-1 were quantified by western blot followed by densitometric scanning and Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios were calculated. T-cells were in vitro tested for oxygen consumption by a respirometric analysis. Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios in untreated MS patients were significantly (p < 0.05) lower than in HCs. Bax/Bcl-2 ratio increased (p = 0.03) and Cyt-c/Bcl-2 ratio showed a trend to increase during the 9 months of GA treatment in MS patients. A reduction of 58% and 59% in oxygen consumption by PBMNCs was evident after GA treatment in vitro or when GA treated patients' cells were compared with those from HCs, respectively. Our findings suggest that GA exerts a regulatory effect on peripheral T lymphocytes through pro-apoptosis mechanisms involving mitochondria and cytosolic proteins.
journal_name
J Neuroljournal_title
Journal of neurologyauthors
Ruggieri M,Avolio C,Scacco S,Pica C,Lia A,Zimatore GB,Papa S,Livrea P,Trojano Mdoi
10.1007/s00415-005-0965-ykeywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
231-6issue
2eissn
0340-5354issn
1432-1459journal_volume
253pub_type
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journal_title:Journal of neurology
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journal_title:Journal of neurology
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doi:10.1007/BF00920572
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journal_title:Journal of neurology
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journal_title:Journal of neurology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2000-04-01 00:00:00
abstract::Although multiple sclerosis (MS) is considered to be an inflammatory demyelinating disease, increasing evidence indicates that it is also an axonal pathology; indeed, studies of experimental allergic encephalitis showed that several neuronal proteins such as synapsins take part in the pathogenesis of the axonal dysfun...
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pub_type: 杂志文章,多中心研究
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journal_title:Journal of neurology
pub_type: 杂志文章
doi:10.1007/s00415-002-0714-4
更新日期:2002-07-01 00:00:00
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doi:10.1007/s00415-019-09574-9
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journal_title:Journal of neurology
pub_type: 杂志文章,评审
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journal_title:Journal of neurology
pub_type: 杂志文章
doi:10.1007/s00415-004-0351-1
更新日期:2004-04-01 00:00:00
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journal_title:Journal of neurology
pub_type: 杂志文章
doi:10.1007/BF00314181
更新日期:1988-05-01 00:00:00
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journal_title:Journal of neurology
pub_type: 杂志文章,评审
doi:10.1007/s00415-005-2016-0
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journal_title:Journal of neurology
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pub_type: 杂志文章
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