Biomedical subjects

Alina Grzanka

Publications and source records attributed to Alina Grzanka.

8 recordsLinked to original sources

PubMed2006

[The cytoskeleton reorganization and differentiation of HL-60 and K-562 human leukemia cell lines].

Microfilaments, microtubules, and intermediate filaments form the cytoskeleton. These substructures play a significant role in cell motility, transport, divisions, differentiation, tumor transformation, and apoptosis. These processes are related with changes in cell shape, in which cytoskeletal proteins take an active part. In non-muscle cells, actin is an essential constituent of microfilaments, tubulin forms microtubules, and vimentin is one of the characteristic proteins of intermediate filaments. The differentiation of cells is associated inseparably with tissue and organ formation, and the induction of malignant cell differentiation can be a method of treatment, especially in hematopoietic steam cell disease therapy. In studies on tumor cell differentiation, agents such as cytokines, retinoids, forbol esters, and vitamin D3 are the most commonly used, and results show these substances may participate in different pathways of signal transduction. Retinoids and vitamin D3 mostly affect gene transcription via nuclear receptors, whereas cytokines act through membrane receptors. The results of studies show actin, tubulin, and vimentin reorganization during the differentiation of leukemia cells, but it remains unknown whether the observed changes are the cause or the result of the differentiation process.

Apoptosis↗

PubMed2006

[Mitochondria and cell death].

In living cells, apoptosis is effected through many different pathways. Programmed cell death (PCD) may proceed with the involvement of membrane receptors, mitochondria, granzyme B, or the endoplasmic reticulum. The mitochondrial pathway is initiated from within the cell as a consequence of changes in reductive potential. It may also be caused by DNA mutation or various disturbances in the cell's metabolism. In some cases, the intrinsic pathway is connected with the extrinsic one, generated by the cell's environment. The central organelle which initiates the intrinsic pathway is the mitochondrion. Changes in the permeability of the mitochondrial outer membrane cause an outflow of cytochrom c, which interacts with cytoplasmic factor Apaf-1 and procaspase 9, in the presence of ATP, and thus triggers the caspase cascade. Apart from cytochrom c, more than 40 regular or executor particles involved in apoptosis might be released from the mitochondrion. These include Smac/DIABLO, Omi/HTR A2, endonuclease G, AIF, and IAP. Moreover, regulatory functions are performed by Bcl-2 family proteins present in the cytoplasm that affect mitochondrial membrane permeability and by heat shock proteins (HSPs), both of these regulating caspase function. The phenomenon of programmed cell death is the main subject of research for many groups of scientists. There are still many aspects which need to be elucidated.

Animals↗

PubMed2006

[Aptamers in clinical diagnostics].

Aptamers are single-stranded DNA or RNA oligonucleotides selected in vitro from combinatorial libraries in a process called SELEX (Systematic Evolution of Ligands by EXponential Enrichment). Aptamers play a role of artificial nucleic acid ligands that can recognize and bind to various organic or inorganic target molecules with high specificity and affinity. They can discriminate even between closely related targets and can be easily chemically modified for radioactive, fluorescent and enzymatic labeling or biostability improvement. Aptamers can thus be considered as universal receptors that rival antibodies in diagnostics as a tool of molecular recognition. To date aptamers have been successively used instead of monoclonal antibodies in flow cytometry, immunochemical sandwich assays and in vivo imaging as well to detect wide range of small or large biomolecules.

Aptamers, Nucleotide↗

PubMed2005

[The role of actin in Alzheimer's disease].

Alzheimer's disease is associated with the formation of extracellular senile plaques and intracellular neurofibrillary tangles. In the neurons of patients, all the morphological features of apoptosis, e.g. blebbing, formation of apoptotic bodies, and chromatin condensation, as well as cytoskeleton reorganization were observed. Actin filaments interact with proteins characteristic of Alzheimer's disease, such as apolipoprotein E, amyloid precursor protein, pressenilin, and tau protein. The degeneration of neurons is associated with the formation of Hirano bodies, which contain actin, cofilin, tubulin, tau protein, and proteins of the MAP family and APP. Actin rods are also observed in postmortal brains of patients with Alzheimer's disease. These 'rods' have been shown to play a role in Hirano body precursors.

Actin Depolymerizing Factors↗

PubMed2005

[The involvement of transglutaminase 2 in autoimmunological diseases].

Transglutaminase 2 (TG-ase 2) is one of the enzymes which catalyzes the deamination and transacylation of proteins. The transfer of a glutamine acyl residue to a lysine amine group of the acceptor protein is one of the posttranslational covalent modifications regulating some polypeptide activities. The control of protein oligomerization by TG-ase 2 is a cause of the formation of detergent-insoluble macromolecular aggregates. These inclusions are present in degenerating cells during, for example, Alzheimer's and Parkinson's disease. Overexpression of TG-ase 2 has been noted in apoptotic cells. Protein reserves in cereals are rich in glutamine, a substrate of TG-ase 2. Deamination of glutamine is the most important reaction for the initiation of the inflammatory process during gluten-dependent disease of the gut (celiac disease). Grains that contain gliadin are a cause of inflammatory reaction in children with intolerance to glutene. Interactions of the TG-ase product-glutamate with antigens of the major histocompatibility complex type II (MHC II, or HLA DQ) cause autoimmunological reaction by CD4+ T lymphocytes. Knowledge of the kinetic and molecular character of TG-ase 2 has contributed to finding peptides to replace gliadin. These molecules do not evoke immunological events.

Animals↗

PubMed2004

Fluorescence and ultrastructural localization of actin distribution patterns in the nucleus of HL-60 and K-562 cell lines treated with cytostatic drugs.

Actin has been studied extensively for decades, but so far its well-defined role has been found localized to the cytoplasm. The present study characterizes the distribution pattern of actin in the nucleus of HL-60 and K-562 cell lines treated with etoposide and doxorubicin. F-actin labeled with TRITC-phalloidin was found in the nucleus in both cell lines independently of the cytostatic drugs used. Using confocal microscopy F-actin is seen in the center of the nucleus showed labeling of the nucleoli by phalloidin. There are also distinct tracts of F-actin seen from nucleoli to the nuclear envelope in some sections. HL-60 cells treated with 200 micro M etoposide and 5, 10 micro M doxorubicin showed cells with characteristic features of apoptosis at the ultrastructural level. Intense immunogold labeling for actin was seen in nucleus of HL-60 cells with compaction and margination of chromatin. In K-562 cells more intense labeling was often found in the cytoplasm of the cells. Positive labeling for actin was not found after control incubations. F-actin is present in the nucleus and there is labeling of nucleoli by phalloidin. The observation at the ultrastructural level suggests that actin can be involved in chromatin reorganization during the process of apoptosis. Increase of labeling at the ultrastructural level in the nucleus of HL-60 cells in relation with compaction and margination of nuclear chromatin might also suggest translocation of actin from cytoplasm to the nucleus in connection with chromatin reorganization.

Actin Cytoskeleton↗

PubMed2003

The influence of etoposide on the distribution of tubulin in human leukemia cell line HL-60.

BACKGROUND: In the last decade there has been increasing interest in cytoskeletal research in relation to important process of cell biology. However, after decades of debate many issues remain unsettled. The aim of our study was to estimate the distribution of tubulin in etoposide-induced HL-60 cells and address the question of whether the reorganization of tubulin may be involved in apoptosis. MATERIAL/METHODS: HL-60 cells were incubated with etoposide (0.02-200 mM/L) for 72 hours. Tubulin was estimated by the indirect immunofluorescence method. TRITC-labeled goat anti rabbit IgG was used to label tubulin. RESULTS: Significant changes occurred in cell morphology of and tubulin organization at 200 mM/L etoposide: large cells, brightly labeled for tubulin, in cytoplasm. At 200 uM/L etoposide, we also observed an increase in apoptotic cells with bright staining for tubulin at the site of apoptotic body formations. Cells with features of apoptosis were frequently seen also at 20 mM/L etoposide. The exposure of cells to 0.02, 0.2, or 2 mM/L etoposide did not result in any visible changes in morphology or tubulin organization. Cell size, the number of viable cells, and the percentage of apoptotic cells correlated significantly with the dose of etoposide (p<0.001). CONCLUSIONS: These results indicate that etoposide promotes changes in the distribution of tubulin in HL-60 cells, depending on the dose, and that the reorganization of tubulin seems to be involved in apoptosis

Antineoplastic Agents, Phytogenic↗

PubMed2002

Distribution of actin in etoposide-induced human leukemia cell line K-562 using fluorescence and immunoelectron microscopy technique.

Localization of actin was studied in erythroleukemic cell line K-562 after treatment with etoposide for 72 hours in a range of concentrations 0.02-200 microM/L. Actin was visualised by fluorescence microscopy and streptavidingold method. These findings indicate that changes in actin after treatment with etoposide were dose-dependent. Significant changes in the cellular distribution of F-actin in K-562 cells were obtained after treatment with 20 and 200 microM/L etoposide. In comparison with control cells, the number of the cells decreased and cells were larger especially at 200 microM/L. F-actin was diffusely distributed throughout the cell at 20 microM/L. Treatment of cells with 200 microM/L etoposide showed F-actin diffusely distributed throughout the cell with local actin assemblies and also at the cell periphery. Immunogold labelling of actin was observed in cells treated with all doses of etoposide and control cells. Labelling was found in the nucleus and also in the cytoplasm. At the ultrastructural level, cells treated with 200 microM/L etoposide showed protrusions at the surface, in which increase of actin was often observed. Etoposide causes changes in actin distribution of K-562 cells, and the changes in expression of actin were not only restricted to cell with features of apoptosis.

Actins↗