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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.
Gregorowicz К., Kosiński S., Traczyk W. Z.: Alteration of brain stem auditory evoked potentials after intracerebroventricular administration of met-enkephalin in rabbits. Acta Physiol. Pol. 1990, 41(1-3): 63-70. Brainstem auditory evoked potentials (BAEPs) were elicited by binaural click stimulation and recorded from the rabbits with chronically implanted electrodes and a cannula for intracerebroventricular injection (i.c.v.). 4000 BAEPs were averaged off line. The registration was carried out before and after i.c.v. injection of met-enkephalin (2.5 or 25 nmol), naloxon (20 μg ), or i.v. injection of morphine (1.0, 2.0, 5.0 mg/kg b.w.). Enkephalin caused shortening of interpeak latency time, naloxon caused its lengthening, while the effect of morphine was not unidirectional. Enkephalin caused increase in the surface area below the negative peaks located in the range of 4.5-7.5 ms from the first positive peak, naloxon caused its decrease while the effect of morphine was also in this respect not unidirectional. It is concluded that opiate receptors are involved in the modulation of the auditory brainstem responses.
Bioactive sphingolipids are important molecules that control wide spectrum of neuronal processes including neurotransmission, synaptic function, cells proliferation and death. Sphingosine kinases (SK1/2) are conserved enzymes that phosphorylate sphingosine to sphingosine-1-phosphate (S1P), which acts as a primary and secondary messenger. S1P binds to 5 receptors and plays essential role in neural signal transduction under physiological and various pathological conditions. Although growing evidence suggests important role of SK1/2 and S1P in neurodegenerative disorders including ischemia, inflammation and Alzheimer’s Disease, till now disturbances of sphingolipids homeostasis in Parkinson’s Disease (PD) remain unknown. Our study try to explain the role of SK1/2 and S1P in molecular mechanism of cell survival and death in model of oxidative stress evoked by neurotoxin 1-methyl-4-phenylpyridinium (MPP+), compound widely used in experimental model of PD. Our data presented that MPP+, comparable to SK inhibition evoked death of human neuroblastoma cells SH-SY5Y in time and concentration dependent manner. These changes are accompanied by increased free radicals concentration in these cells. Reduced level of SK1 protein was detected in SH-SY5Y cells after 24h exposure to MPP+ comparing to control. Moreover S1P pretreatment enhanced survival of these cells and protein level of SK1 comparing to MPP+ treated cells. Our data indicated that MPP+ evoked neuronal death is mediated by SK1/2 inhibition and altered sphingolipids signaling. These molecular events lead to caspase dependent apoptotic cells death and poly(ADP-ribose) polymerase-1 (PARP-1) degradation. All above results presented the alteration of sphingolipid biostat in experimental model of PD and suggested that S1P can offer novel, protective strategy.Supported by NCN Grant 5870/B/PO1/2011/40
Due to its natural properties, Trichoderma reesei is commonly used in industry-scale production of secretory proteins. Since almost all secreted proteins are O-glycosylated, modulation of the activity of enzymes of the O-glycosylation pathway are likely to affect protein production and secretion or change the glycosylation pattern of the secreted proteins, altering their stability and biological activity. Understanding how the activation of different components of the O-glycosylation pathway influences the glycosylation pattern of proteins and their production and secretion could help in elucidating the mechanism of the regulation of these processes and should facilitate creation of engineered microorganisms producing high amounts of useful proteins. In this review we focus on data concerning Trichoderma, but also present some background information allowing comparison with other fungal species.
The effect of the sodium cyanate-induced carbamylation (carbamoylation) of proteins in erythrocytes was studied using spin labelling and spectrophotometric methods. The experiments were conducted in whole blood and in erythrocytes in phosphate buffer using 25 mmol/L of sodium cyanate. Lipid membrane fluidity was determined using three spin-labelled fatty acids: 5-, 12- and 16-doxylstearic acids (5-DS, 12-DS, 16-DS). Internal viscosity was measured with Tempamine, using also EPR spectroscopy. Osmotic fragility was determined spectrophotometrically. Incubation of whole blood with sodium cyanate led to an increase in lipid membrane fluidity in the deeper region of the lipid layer, indicated by 12- and 16-doxylstearic acid, and a decrease near the surface (5-DS). Statistically significant results were obtained for the internal viscosity and osmotic fragility of erythrocytes. An increase in internal viscosity and increase in osmotic fragility were found in erythrocytes after incubation of whole blood, as well as in erythrocytes incubated with sodium cyanate in buffer. Alterations in internal viscosity were stronger in erythrocytes incubated with sodium cyanate in blood than in erythrocytes in the buffer. On the other hand, higher osmotic fragility was observed for erythrocytes in the buffer.
Chronic-degenerative diseases (CDD) recognise a variety of exogenous and endoge­nous risk factors interacting with the organism for many years before disease onset. We applied genomic and postgenomic molecular analyses in experimental models characterised by different contribution of exogenous and endogenous CDD risk fac­tors. Exposure of mice to halogen light for 28 days resulted in induction of cyclobutane dimers and oxidative DNA damage in the skin. Evaluation of postgenomic alterations by cDNA arrays revealed upregulation of DNA repair pathways, increased cell divi­sion rate and protooncogenes transcription, resulting in skin tumors, 1 year later. Exposure of p53-/+ mutant mice to cigarette smoke (CS) for 28 days induced DNA adducts formation in the lung. Postgenomic alterations included decreased apoptosis and increased cell division, as compared to CS-exposed wild type mice. These phenom­ena resulted in lung tumors, 9 months later. Transplacental exposure of mouse foetuses to cigarette smoke induced DNA adduct formation in the liver. cDNA arrays analyses demonstrated decreased cell division, apoptosis increase, and tissue hypoxia. These phenomena resulted in growth retarda­tion of the whole organism. Molecular alterations were investigated in human trabecular meshwork, the non-replicating ocular epithelia involved in the pathogenesis of chronic degenerative glaucoma. Results indicate increased oxidative DNA damage in glaucoma patients as compared to unaffected controls.
The state of the vascular system of the mother and of placenta is known to exert a great influence on intrauterinal development of the fetus. Pre-eclampsia is the most common pathological syndrome connected with pregnancy. Since collagen is one of the main constituents of the vessel wall a comparison was made with collagen content and its molecular polymorphism in umbilical cord veins of newborns from healthy and pre-eclamptic mothers. It was found that umbilical cord veins of newborns from moth­ers with pre-eclampsia contained 18% less collagen than those of the newborns from normal pregnancies. This decrease was accompanied by a slight decrease of collagen solubility, but all its types (I, III, IV, V and VI) were present. However, the umbilical vein wall of newborns from mothers with pre-eclampsia contained relatively less of type I and more of type III collagen than the normal umbilical cord. These differences may be connected with a disturbance of blood flow in fetus of a woman with pre-eclampsia.
Previously, autism spectrum disorder (ASD) has been identified mainly by social communication deficits and behavioral symptoms. However, a link between behaviors and learning process in the brain of animal model of autism remained largely unexplored. Particularly, spontaneous neural signaling in learning-related brain areas has not been studied. This study investigated local field potential (LFP) of the hippocampus (HP), the olfactory bulb (OB) and the medial prefrontal cortex (mPFC) in mice prenatally exposed to valproic acid (VPA) on gestational day 13. Adult male Swiss albino mouse offspring implanted with intracranial electrodes were used. VPA-exposed mice exhibited ASD-associated behaviors. Hippocampal LFP analysis revealed that VPA group significantly increased low gamma activity (25–45 Hz) during awake immobility. Regression analyses confirmed positive correlations between locomotor speed and hippocampal theta oscillations in control but not VPA group. VPA group exhibited increases in delta (1–4 Hz) and beta (25–35 Hz) activities in OB during awake immobility and active exploring, respectively. Moreover, significantly increased and decreased coherences between HP and OB of VPA animals were seen within gamma (active exploration) and theta (awake immobility) ranges, respectively. In addition, significant increase in coherence between HP and mPFC was seen within delta range during active exploration. In addition to three ASD symptoms, VPA animals also exhibited differential patterns of olfacto-hippocampal LFP, altered locomotor speed-related hippocampal theta activities and distinct interplays between HP and learning-related brain areas. The altered olfacto-hippocampal and medial prefrontal cortex-hippocampal networks may underlie impairments in autism mouse model.
Background. The abundance of club cells in epidermal tissue of fishes in the superorder Ostariophysi is a poorly understood phenomenon. Previous results have suggested that epidermal club cells have a generic role in response to injury and that they display intense phagocytotic activity, having an anti-parasitic function in the host. Earlier works suggested that club cells are usually located in the middle of the epidermis and that they do not communicate with the epidermal surface or do it only when the epidermis has been ruptured by predation. The presently reported study focused on the alterations of club cell activity in carp epidermis induced by ectoparasite, Ichthyophthirius multifiliis.We hoped that our observations would help to understand the function(s) of these cells. Materials and methods. This study was based on 200 four-month old common carp, Cyprinus carpio L., with mean body weight of 65 ± 5 g. The fish were experimentally infected with theronts of Ichthyophthirius multifiliis. In sequential days post infection, samples of fins and body skin were collected for histological and histochemical examination. The correlation between club cell densities and mucous cell densities was analysed using Pearson correlation analyses. Results. A local reduction of mucous cells occurred after theront invasion-induced proliferation, and increased club cell density around the parasite during the growth of trophonts. After parasites left the skin due to salt-water treatment, a decrease in the number of club cells was detected. During reinvasion the decrease in parasite activity in areas of club cells proliferation was not noted. It was found that giant mature club cells were opened on the surface. Conclusion. Club cells have no anti-parasitic function against I. multifiliis and these mature cells released their viscous secretion into water. The high density of club cells in the epidermis compensates an overall low density or absence of mucous cells. As it can be hardly concluded that the function of club cells is phagocytic removal of cell debris, an integrated research on mucosal immune mechanisms, as well as studies on epidermal tissue responses on product(s) released by club cells (“alarm substance cells”) should be carried out in the future.
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