Increased vulnerability to oxidative stress in lymphocytes from SAD and FAD patients

• Autorzy: Bialopiotrowicz . , Kuzniewska B. , Kuchamakova N. , Kuznicki J. , Wojda U.
• Języki publikacji: EN

Abstrakty

EN

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in which certain molecular changes are observed not only in neurons but also in peripheral cells. Growing evidence suggests that AD post-mitotic neurons exhibit increased apoptotic response to oxidative stress, mitochondria dysfunction and calcium dyshomeostasis. We hypothesized that some of these alterations could be observed in peripheral lymphocytes and studied for potential diagnostic purposes. We analyzed apoptotic response to the redox stress evoked by 2-deoxy-Dribose in immortalized lymphocytes from 18 patients with sporadic AD (SAD), from 2 familial AD (FAD) patients with novel mutations in presenilin 1: P117R and I213F, and from 20 agematched healthy individuals. Using two independent fl ow cytometry methods for quantifi cation of apoptosis, we found that SAD and FAD lymphocytes show enhanced apoptotic response to the redox stress. This apoptotic response was accompanied by decline in mitochondrial membrane potential measured with JC-1 as well as by increased activities of caspase 9 and caspase 3. However, no changes in the expression of two calcium-binding proteins: calmyrin 1 and calreticulin were observed. This study emphasizes that increased susceptibility to redox stress and associated upregulation of mitochondrial apoptotic pathway is characteristic not only for AD neurons, but also for AD lymphocytes. Thus, human lymphocytes could be used in further studies on AD pathogenesis.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.341

Twórcy

autor

Bialopiotrowicz .

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Kuzniewska B.

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Kuchamakova N.

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Kuznicki J.

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Wojda U.

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland