Wyniki wyszukiwania - Biblioteka Nauki

1

Curcumin induces cell death without oligonucleosomal DNA fragmentation in quiescent and proliferating human CD8+ cells

100%

Magalska A. , Brzezinska A. , Bielak-Zmijewska A. , Piwocka K. , Mosieniak G. , Sikora E.

Acta Biochimica Polonica

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2006

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tom 53

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nr 3

531-538

EN

Cytotoxic CD8+ cells play an important role in determining host response to tumor, thus chemotherapy is potentially dangerous as it may lead to T cells depletion. The purpose of this study was to elucidate the propensity of quiescent and proliferating human CD8+ cells to undergo cell death upon treatment with curcumin, a natural dye in Phase I of clinical trials as a prospective chemopreventive agent. Methods: We treated human quiescent or proliferating CD8+ cells with 50 µM curcumin or irradiated them with UVC. Cell death symptoms such as decreased cell viability, chromatin condensation, activation of caspase-3 and specific DFF40/CAD endonuclease and oligonucleosomal DNA fragmentation were analyzed using MTT test, microscopic observation, Western blotting and flow cytometry. Results: Curcumin decreased cell viability, activated caspase-3 and decreased the level of DFF45/ICAD, the inhibitor of the DFF40/CAD endonuclease. However, this did not lead to oligonucleosomal DNA degradation. In contrast, UVC-irradiated proliferating, but not quiescent CD8+ cells revealed molecular and morphological changes characteristic for apoptosis, including oligonucleosomal DNA fragmentation. Curcumin can induce cell death in normal human lymphocytes both quiescent and proliferating, without oligonucleosomal DNA degradation which is considered as a main hallmark of apoptotic cell death. Taking into account the role of CD8+ cells in tumor response, their depletion during chemotherapy could be particularly undesirable.

2

Alterations in cell nuclei during apoptosis

75%

Rogalinska M.

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nr 4

EN

Apoptosis is a genetically programmed phenomenon that aids in maintaining homeostasis in multicellular organisms. The characteristic morphological features of apoptosis are highly conservative and are dependent on the cell type and the apoptotic inducer. The nuclear events occurring during apoptosis include changes at the molecular level (i.e. DNA cleavage, modifications of nuclear polypeptides, and proteolysis of several proteins important for cell maintenance), and, consequently, alterations at the morphological level (i.e. chromatin condensation, nuclear shrinkage, DNA fragmentation and apoptotic body formation). These events are still not fully understood. It is very probable that a progressive decrease in pH could also be an essential factor for the induction of nuclease and protease activities, and an important element of the optimal conditions for their function. This review details the current state of knowledge on apoptotic nuclear events, with particular focus on the proteins involved in the execution of apoptosis in cell nuclei, and on the differences in substrate cleavage profiles for different types of cell undergoing celi death.

3

Overexpression of fused Cucurbita pepo 14-3-3 polypeptide with MBP in E.coli modifies the apoptotic-like effects in the cells

75%

Markiewicz E. , Wilczynski G. , Kulma A. , Feiga I. , Filipski J. , Szopa J.

Cellular and Molecular Biology Letters

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1997

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tom 02

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nr 2

4

Combined effects of doxorubicin and STI571 on growth, differentiation and apoptosis of CML cell line K562

63%

Jakubowska J. , Stasiak M. , Szulawska A. , Bednarek A. , Czyz M.

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tom 54

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nr 4

839-846

EN

STI571 (imatinib mesylate; Gleevec®) is an inhibitor that targets the tyrosine kinase activity of Bcr-Abl present in chronic myelogenous leukemia (CML) cells. Some preclinical studies have demonstrated that the combination of STI571 with chemotherapeutic drugs results in enhanced toxicity in Bcr-Abl-positive leukemias. We investigated the potential benefit of using STI571 to down-regulate Bcr-Abl activity for the enhancement of doxorubicin anti-proliferative action in K562 cell line derived from blast crisis of CML. At low concentrations of both drugs (40 nM doxorubicin combined with STI571 in the range of 100–150 nM), the antiproliferative effects were mainly due to cellular differentiation as assessed by benzidine staining for hemoglobin synthesis level and real-time PCR for γ-globin expression. Higher concentrations of STI571 used in combinations with doxorubicin caused mainly apoptosis as shown by DNA degradation and nuclear fragmentation visualized by fluorescence microscopy after DAPI staining, changes in cell morphology observed after Giemza-May Grünwald staining and cellular membrane organization estimated by flow cytometry after Annexin V staining. As compared with either drug alone, cotreatment with STI571 and DOX induced stronger cellular responses. A low concentration of STI571 in combination with a low concentration of DOX might be tested as an alternative approach to increasing the efficacy of chemotherapy against CML

5

Non-Abeta component of Alzheimer's disease amyloid and amyloid beta peptides evoked poly(ADP-ribose) polymerase-dependent release of apoptosis-inducing factor from rat brain mitochondria

63%

Adamczyk A. , Czapski G. A. , Jesko H. , Strosznajder R. P.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 2

5-13

EN

Amyloid beta peptide (Aß) and non-Aß component of Alzheimer’s disease amyloid (NAC) are involved in pathomechanism of Alzheimer's Disease (AD) and are deposited in the AD brain in the form of senile plaques. However, the mechanism of their neurotoxicity is not fully understood. In this study the sequence of events involved in NAC and Aß peptides evoked toxicity was investigated in brain slices, synaptosomes and in subcellular fractions. Radio-, immunochemical, spectrophotometrical methods and DNA electrophoresis were used in this study. Our data indicated that Aß 1-40 (25 µM) and NAC (10 µM) peptides induced liberation of free radicals and massive DNA damage that lead to activation of DNA bound enzyme poly(ADP-ribose) polymerase-1 (PARP-1). In consequence of these processes apoptosis-inducing factor (AIF) was released from mitochondria and was translocated to nucleus. The inhibitor of PARP, 3-aminobenzamide significantly decreased AIF release from mitochondria and its translocation. Both peptides under the investigated conditions had no effect on caspase-3 activity. Our data indicated that Aß and NAC peptides stimulate AIF-dependent apoptotic pathway that seems to be caspase independent process. The inhibition of PARP-1 may protect the brain against Aß and NAC toxicity.

6

Pterostilbene induces accumulation of autophagic vacuoles followed by cell death in HL60 human leukemia cells

51%

Siedlewska-Kroplewska K. , Jozwik A. , Boguslawski W. , Wozniak M. , Zauszkiewicz-Pawlak A. , Spodnik J. H. , Rychlowski M. , Kmiec Z.

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nr 5