Processes of adult neurogenesis can be influenced by environmental factors. Here, we investigated the effect of microwave radiation (MWR) on proliferation and cell dying in the rat rostral migratory stream (RMS) - a migration route for the neuroblasts of the subventricular zone. Adult and juvenile (two weeks old) rats were exposed to a pulsed-wave MWR at the frequency of 2.45 GHz for 1 or 3 h daily during 3 weeks. Adult rats were divided into two groups: without survival and with two weeks survival after irradiation. Juvenile rats survived till adulthood, when were tested in the light/dark test. Proliferating cells in the RMS were labeled by Ki-67; dying cells were visualized by Fluoro-Jade C histochemistry. In both groups of rats irradiated as adults we have observed significant decrease of the number of dividing cells within the RMS. Exposure of juvenile rats to MWR induced only slight decrease in proliferation, however, it strikingly affected cell death even two months following irradiation. In addition, these rats displayed locomotor hyperactivity and decreased risk assessment in adulthood. Our results suggest that the long-lasting influence of radiation is manifested by affected cell survival and changes in animals´ behavior., A. Raček, K. Beňová, P. Arnoul, M. Závodská, A. Angelidis, V. Cigánková, V. Šimaiová, E. Račeková., and Obsahuje bibliografii
Bcl-2/E1B-19K-interacting protein 3 (BNIP3) is a member of the apoptotic B-cell lymphoma-2 family that regulates cell death. Although BNIP3 targeted normally to the mitochondrial outer membrane by its transmembrane domain was originally considered to be essential for its pro-apoptotic activity, accumulating evidence has shown that BNIP3 is localized to endoplasmic reticulum at physiological conditions and that forced expression of BNIP3 can initiate cell death via multiple pathways depending on the subcellular compartment it targets. Targeting BNIP3 to endoplasmic reticulum has been shown to participate in cell death during endoplasmic reticulum stress. However, the molecular events responsible for BNIP3-induced cell death in the endoplasmic reticulum remain poorly understood. In the present study, the transmembrane domain of BNIP3 was replaced with a segment of cytochrome b5 that targets BNIP3 into endoplasmic reticulum, which induced cell death as effectively as its wild-type molecule in the SW480 cell line (colon carcinoma). Furthermore, a pan-caspase inhibitor, z-VAD-fmk, and PD150606, a specific calpain inhibitor, both significantly suppressed the endoplasmic reticulum-targeted BNIP3- induced cell death. These results suggest that endoplasmic reticulum-targeted BNIP3 induced a mixed mode of cell death requiring both caspases and calpains.
Several neurodegenerative conditions, such as Alzheimer’s disease and Parkinson’s disease, or vascular dementia and cognitive impairment, are associated with mild hyperhomocysteinemia. Hyperhomocysteinemia is defined as an increas e of the homocysteine (Hcy) level beyond 10 μM. Although the adverse effect of Hcy on neurons is well documented, knowledge about the impact of this amino acid on glial cells is missing. Therefore, with the aim to evaluate the neurotoxic properties of Hcy on glial cells, we used a glioblastoma cell line as a study model. The viability of cells was assayed biochemically and cytologically. At a concentration around 50 μM in the culture medium D,L -Hcy induced cell death. It is noteworthy that Hcy induces cell death of human glial cells at concentrations encountered during mild hyperhomocysteinemia. Therefore, we propose that Hcy -induced impairment of neuronal functions along with damage of glial cells may contribute to the etiopathogenesis of neurodegenerative diseases associated with hyperhomocysteinemia., H. Škovierová, S. Mahmood, E. Blahovcová, J. Hatok, J. Lehotský, R. Murín., and Obsahuje bibliografii
The purpose of this study was to investigate the occurrence and time-course of apoptosis in soleus skeletal muscle during the first 48 hours of unloading. Fifty Charles River mice were randomly divided into five groups (n=10 each) according to the time of hindlimb suspension (HS). Mice we re suspended for 0 (Control), 6 (6HS), 12 (12HS), 24 (24HS), and 48 hours (48HS). Soleus muscle atrophy was confirmed by a significant decrease of 20 % in muscle-wet weight and of 5 % in the ratio protein concentration/muscle wet-weight observed after 48 hours of unloading. The apoptotic index, the AIF (apoptosis-inducing factor) and p53 expression presented th eir uppermost value (304 %, 241 % and 246 %, respectively) at 24HS, and were preceded by the highest activity of caspase-3 and -8 at 12HS (170 % and 218 %, respectively) and of Bax/Bcl-2 content at 6HS (160 %). There were no marked ultrastructural alterations until 24 hours of simulated weightlessness. Lysosomal autophagic activity and infiltration of phagocytic cells were observed at 24HS and 48HS and might have contributed to the degenerative changes noticed in both groups. Though not consistently supported by morphological evidences, the biochemical parameters sustain the concept that the occurrence of apoptosis parallels the soleus atrophic response in its early phase., R. Ferreira, M. J. Neuparth, R. Vittorino, H. J. Appell, F. Amado, J. A. Duarte., and Obsahuje bibliografii a bibliografické odkazy
Sodium borocaptate (BSH, Na2Bi2HnSH), a slow neutron-capture compound, was injected into the left forebrain ventricle of 1-week-old rats (150 fig BSH/3 p\ phosphate buffered saline). After 90 min, the animals were irradiated by epithermal neutrons (LVR-15 nuclear reactor in Řež near Prague, flux density 8.8 x 107 neutrons cm-2 s'1, 8 MW reactor power, 8.2 cGy/min) for 5,10 or 20 min. The brains were examined histologically 8 h after irradiation. In animals irradiated for 5 to 10 min (41 and 82 cGy-Eq, respectively) lethal damage of cells was found in the external granular layer of the cerebellum and the subependymal layer of the forebrain. Irradiation for 20 min (164 cGy-Eq) caused more extensive destruction of cell populations in these regions and, in addition, dead cells appeared also in the more differentiated postmitotic compartments, namely the deeper layers of the cerebellum, layers II/III of the cerebral cortex and corpus callosum. In the forebrain periventricular layer, the extent of cell damage was declining towards the olfactory bulbs. In intact animals, as well as in those injected only with the 150 p\ phosphate buffered saline, the radiation damage was low and limited only to the most sensitive dividing populations of the cerebellum and the forebrain. The study demonstrates a differentiation-dependent damage of the rat brain cells by alpha particles and presents a simple model for evaluation of the biological effectiveness of slow neutron beams constructed for neutron-capture therapy of tumors.
Although statins exert non-lipid cardioprotective effects, their influence on cell death is not fully elucidated. For this purpose, we investigated whether simvastatin treatment (S, 10 mg/kg, 5 days) is capable of mitigating ischemia/reperfusion-induced (IR) apoptosis in the isolated rat hearts, which was examined using immunoblotting analysis. In addition, the content of signal transducer and activator of transcription 3 (STAT3) and its active form, phosphorylated STAT3 (pSTAT3-Thr705), was analyzed. Simvastatin induced neither variations in the plasma lipid levels nor alterations in the baseline content of analysed proteins with the exception of upregulation of cytochrome C. Furthermore, simvastatin significantly increased the baseline levels of pSTAT3 in contrast to the control group. In the IR hearts, simvastatin reduced the expression of Bax and non-cleaved caspase-3. In these hearts, phosphorylation of STAT3 did not differ in comparison to the non-treated IR group, however total STAT3 content was slightly increased. The improved recovery of left ventricular developed pressure co-existed with the increased Bcl- 2/Bax ratio. In conclusion, pleiotropic action of statins may ameliorate viability of cardiomyocytes by favouring the expression of anti-apoptotic Bcl-2 and downregulating the proapoptotic markers; however STAT3 does not seem to be a dominant regulator of this anti-apoptotic action of simvastatin., T. Rajtík, ... [et al.]., and Obsahuje seznam literatury