Preferencje help
Polish version English version Język
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 2

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
1

Cell cycle malfunctions in lymphocytes from sporadic Alzheimer’s disease patients

100%
Bialopiotrowicz E., Kuzniewska B., Kochamakova-Trojanowska N. M., Barcikowska M., Kuznicki J., Wojda U.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr 1
Alzheimer’s disease (AD) constitutes one of the leading causes of disability with enormous socioeconomic costs. Most of AD cases occur sporadically and have unknown etiology (SAD). The Abeta peptide deposition in neuritic plaques is one of AD major hallmarks. Nevertheless, the role of Abeta as a primary driver in AD progression arouses controversy. Mounting evidence suggests that neurodegeneration results from the cell cycle reentry occurring in AD neurons. Recent data indicate that some of the cell cycle changes can be also observed in peripheral cells. Thus, our aim was to investigate whether any cell cycle abnormalities occur in transcriptome or proteome of lymphocytes from SAD patients. This study was performed in immortalized lymphocytes from 18 SAD patients and 26 healthy age-matched individuals. PCR arrays experiments showed that 43% of the 90 investigated cell cycle genes were down-regulated in SAD, whereas 4% were up-regulated comparing to control lymphocytes. Since most significant changes referred to the genes engaged in G1/S control, we assessed the levels of key proteins involved in G1/S transition with immunobloting. The most striking difference occurred in p21 protein level, which was significantly elevated for SAD in respect to controls. Furthermore, we measured distribution of cells in G1, S and G2/M cell cycle phases using flow cytometry. Our results showed increased % of cells in G1 phase with adequate decrease in % of cells in S phase for SAD lymphocytes. However, estimation of proliferation rate for SAD and control lymphocytes revealed no significant differences. We therefore used the following methods to assess the lengths of G1 and S phases: flow cytometry analysis of PI-labeled cells after nocodazole treatment and BrdU pulse chase labeling. SAD lymphocytes indicated significant prolongation of G1 phase and simultaneous shortening of S phase. In addition, treating the cells with gamma-secretase inhibitor L685,458 did not affect the observed cell cycle dysregulations, which highlighted that the impairments of cell cycle in SAD lymphocytes are not linked to gamma-secretase activity. Taken together, this study emphasizes that disturbances in the cell cycle control are common for AD neurons as well as SAD lymphocytes. Thus, human lymphocytes could be used in further studies on AD pathogenesis and diagnostics
2

The role of cyclin-dependent kinase 5 in pathomechanism of Alzheimer’s disease

100%
Czapski G. A., Maruszak A., Styczynska M., Zekanowski C., Safranow K., Bialopiotrowicz E., Strosznajder J. B.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr 1
Alteration of Amyloid Precursor Protein (APP) processing, leading to overproduction of Amyloid beta (Ab), and hyperphosphorylation of Microtubule-Associated Protein (MAP) tau remain in the center of pathomechanism of Alzheimer’s disease (AD). The recent data indicated that oligomeric form of Aβ is responsible for memory impairment in AD. Also deregulation of protein phosphorylation processes plays an important role in AD pathology. Cyclin-Dependent Kinase 5 (CDK5) is responsible for aberrant phosphorylation of both MAP tau and APP. Moreover, CDK5 may also phosphorylate other proteins potentially involved in AD pathogenesis, i.a. Glycogen Synthase Kinase-3b (GSK-3b), NMDAR, p53. The aim of the present study was to analyze the participation of CDK5 in cell death processes occurring in PC12 cells overexpressing APP. As a model, we used cells transfected with human wild-type APP (APPwt) and human APP with Swedish mutation (APPsw). Real-time PCR and Western blotting were used for analysis of expression and phosphorylation of CDK5, CDK5R1, CDK5R2, GSK-3β. Cytotoxicity was evaluated by MTT and LDH tests. To determine the role of CDK5 in AD patients, the association of human CDK5 gene with AD risk was analyzed. Our data demonstrated enhanced cell death and cell cycle disturbances in PC12 cells transfected with APP gene, comparing to control PC12 cells. Real-time PCR analysis indicated increased level of mRNA for CDK5 gene in APPsw cells. Significantly decreased phosphorylation of CDK5 on Tyr15 was observed in APPwt and APPsw cells, what can be responsible for lowering of Cdk5 activity. Moreover, Cdk5-dependent phosphorylation of GSK-3β on Ser9 was also decreased, what can be responsible for GSK-3β activation, hyperphosphorylation of MAP tau and alteration of cell function. Our genetic analysis indicated that there is no association between polymorphism of CDK5 gene and the risk of AD in investigated Polish population (178 healthy controls, 71 EOAD and 204 LOAD cases). Significant differences in serum level of cholesterol, LDL, vitamin B12 and homocysteine between AD patients and healthy controls were found, but there was no association of tested CDK5 genotypes with biochemical parameters. These results indicated the important role of CDK5 - GSK-3β interplay in pathomechanism of AD. This study was supported by MSHE Grant N N401 014635
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.