Neuronal intracellular transport is performed by motor proteins, which deliver vesicles, organelles and proteins along cytoskeletal tracks inside the neuron. We have previously shown that the anesthetic propofol causes dose- and time-dependent, reversible retraction of neuronal neurites. We hypothesize that propofol alters the vesicular transport of cortical neurons due to this neurite retraction. Primary cultures of co-cultivated rat cortical neurons and glial cells were exposed to either 2 µM propofol, control medium or the lipid vehicle, in time-response experiments. Reversibility was tested by washing propofol off the cells. The role of the GABAA receptor (GABAAR) was assessed with the GABAAR antagonist gabazine. Vesicles were tracked using differential interference contrast video microscopy. Propofol caused a retrograde movement in 83.4±5.2% (mean±S.E.M.) of vesicles, which accelerated over the observed time course (0.025±0.012 µm·s-1). In control medium, vesicles moved predominantly anterograde (84.6±11.1%) with lower velocity (0.011±0.004 µm·s-1). Cells exposed to the lipid vehicle showed the same dynamic characteristics as cells in control medium. The propofol-induced effect on vesicle transport was reversible and blocked by the GABAAR antagonist gabazine in low concentration. Our results show that propofol causes a reversible, accelerating vesicle movement toward the neuronal cell body that is mediated via synaptic GABAAR. We have previously reported that propofol initiates neurite retraction, and we propose that propofol causes vesicle movement by retrograde flow of cytoplasm from the narrowed neurite.
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Metformin is an orally administered drug that lowers blood glucose and improves insulin sensitivity in patients with non insulin-dependent diabetes. Although the antihyperglycemic effect of metformin has been extensively studied, its cellular mechanism(s) of action (including the effect on enterocyte) remains to be defined. This study was designed to examine the effect of metformin on glucose transporters in enterocyte. Na+-dependent glucose transporter-1 (SGLT-1) activity was followed as glucose-induced short-circuit current (Isc) in Ussing chambers. The effect of metformin (10 µmol/L, 3 min) on transmural glucose transport was studied in isolated rat jejunal loops. Its impact on abundance of transporters SGLT-1 and GLUT2 in jejunal brush border membranes (BBM) and its effect on the phosphorylation of AMP-activated protein kinase (AMPK) 2 subunit was studied by western blot. Acute effect of metformin was also measured in vivo by oral glucose tolerance test (OGTT). Metformin markedly inhibited glucose-induced Isc (~77%) after mucosal addition. In addition, metformin reduced the glucose-induced abundance of SGLT-1 in BBM and increased those of GLUT2, concomitantly increasing the phosphorylation of intracellular AMPK2. This effect of metformin was also observed using non-metabolizable sugar 3-O-methyl glucose. Transmural glucose transport measured in vitro was increased by 22% under metformin. Finally, oral metformin markedly increased glucose tolerance in OGTT. In conclusion, metformin slightly increases intestinal glucose absorption by inducing a re-distribution of glucose transporters in BBM through AMPK control in enterocyte. In addition to its action to other splanchnic tissues, this could constitute a peripheral signal contributing to the beneficial effect of metformin on glucose tolerance.
Cell proliferation and differentiation is a complex process involving many cellular mechanisms. One of the best-studied phenomena in cell differentiation is erythrocyte development during hematopoiesis in vertebrates. In recent years, a new class of small, endogenous, non-coding RNAs called microRNAs (miRNAs) emerged as important regulators of gene expression at the post-transcriptional level. Thousands of miRNAs have been identified in various organisms, including protozoa, fungi, bacteria and viruses, proving that the regulatory miRNA pathway is conserved in evolution. There are many examples of miRNA-mediated regulation of gene expression in the processes of cell proliferation, differentiation and apoptosis, and in cancer genesis. Many of the collected data clearly show the dependence of the proteome of a cell on the qualitative and quantitative composition of endogenous miRNAs. Numerous specific miRNAs are present in the hematopoietic erythroid line. This review attempts to summarize the state of knowledge on the role of miRNAs in the regulation of different stages of erythropoiesis. Original experimental data and results obtained with bioinformatics tools were combined to elucidate the currently known regulatory network of miRNAs that guide the process of differentiation of red blood cells.
The high level of cadmium in the abdominal muscle of the brown shrimp Crangon crangon is due to the serious pollution of the water in the Gulf of Gdańsk. The inhibition of malic enzyme (ME) activity by cadmium, and in consequence the reduced formation of NADPH, could interfere with cellular mechanisms for detoxifying the organism and reducing oxidative stress. The reduced glutathione (GSH) concentration in the abdominal muscle of C. crangon was calculated to be 5.8 mM. The objective of this study was to evaluate the part played by GSH in the effect of cadmium on the activity of NADP-dependent malic enzyme from abdominal muscles of brown shrimps. This enzyme is activated by certain divalent cations (Mg, Mn). The results demonstrate that cadmium inhibits ME activity from shrimp muscle, and that GSH and albumin can reduce this cadmium-inhibited NADP-dependent malic enzyme activity.
Results of micromorphological and histological studies of larvae of Trichinella Spiralis and T. pseudospiralis, as weil as, muscles, liver and small intestine of the rat-host before and after biostimulator administration of phytohemagglutinin and phytoanthelminthic were presented. It has been established that rats with Trichinella larvae of both species developed unspecific allergic angiomyositis, hepatitis, cholangitis, and erosio-haemorrhagic enterocolitis in the host's organism on the 35th day after infection. Furthermore, processes of compensatory hypertrophy, that support the host's (rats) homeostasis, on cell and tissue levels, were observed at histodestructional and morphofunctional deficiency. lt has been revealed that phytohemagglutinin, biostimulator injected into the host's organism before infection, is of immunostimulating nature and partially destroys the larvae of Trichinella. The phytoanthelminthic produces a significant trichinellocide effect: RNA synthesis and glycogen is intensified in the organs of the treated animals, their pathomicromorphogenesis weakened, and their compensatory and regenerative processes were observed. The combined use of the phytohemagglutinin and phytoanthelminthic fails to intensify the mentioned effect.