Wyniki wyszukiwania - Biblioteka Nauki

1

Quantum mechanical approach to sphere beds in the container-packing fractions and radial distribution function

100%

Pietrow M. , Gozdz A.

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nr 1

2

Quantum mechanical approach to randomly-packed beds of spheres in the container

100%

Gozdz A. , Pietrow M.

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nr 2

3

GSK3 regulates Arc protein expression in primary neuronal culture-possible applications for synaptic plasticity

80%

Gozdz A. , Cymerman L. , Urbanska M. , Jaworski J.

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nr Suppl.1

EN

GSK3 alpha/beta (Glycogen Synthase Kinases alpha/beta) are serine/threonine kinases ubiquitously expressed in the nervous system. GSK3’s appear to be critical for LTD formation and overactivation of GSK3 inhibits LTP expression. Here we report that GSK3 regulate expression of Arc/Arg3.1 protein (Activity Regulated Cytoskeleton Associated Protein/Activity Regulated Gene 3.1), involved in diverse forms of synaptic plasticity, including LTP, LTD and homeostatic plasticity. We hypothesize that Arc could be one of the putative GSK3 effectors in neurons. The combination of low dose NMDA and GSK3 inhibitors upregulated Arc expression at the protein but not at the mRNA level. Recombinant Arc protein is phosphorylated in vitro by GSK3 beta. Currently, we are characterizing the mechanism of GSK3-dependent Arc degradation. We also observed that the co-treatment of neurons with GSK3 inhibitors and NMDA induced alterations in the dendritic spine morphology. We are employing shRNA technology to determine if Arc contributes to the observed alterations in dendritic spines morphology and what is the role of GSK3-dependent Arc degradation in different forms of synaptic plasticity. Supported by 7FP EU grant 223276 “NeuroGSK3” and NCN 05397 grant from National Center for Science.

4

Vasopressin V1a, V1b and V2 receptors mRNA in the kidney and heart of the renin transgenic TGR(mREN2)27 and sprague dawley rats

70%

Gozdz A. , Szczepanska-Sadowska E. , Szczepanska K. , Maslinski W. , Luszczyk B.

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nr 3

EN

Vasopressin plays significant role in regulation of blood pressure by means of V1 and V2 receptors, however regulation of synthesis of these receptors in hypertension is only poorly recognized. The puropose of the present study was to compare expression of V1a, V1b and V2 vasopressin (R) mRNA in the renal cortex, renal medulla and the heart of hypertensive renin transgenic TGR(mRen2)27 rats (TGR) and of their parent normotensive Sprague Dawley (SD) strain. The study was performed on 12 weeks old TGR and SD rats. Competitive PCR method was used for quantitative analysis of V1a, V1b and V2 receptors mRNA in fragments of renal cortex, renal medulla and apex of the left ventricle of the heart. In both strains expression of V1aR and V2R mRNA was significantly greater in the renal medulla than in the renal cortex. In the renal medulla but not in the cortex expression of V1aR mRNA was significantly greater in TGR than in SD rats. V2R mRNA expression was similar in the renal cortex and renal medulla of both strains. V1aR mRNA was well expressed in the heart of SD and TGR rats, however there was no significant difference between these two strains. V2R mRNA was not present in the heart. V1b R mRNa could not be detected either in the kidney or in the heart. The results provide evidence for specific increase of expression of V1a receptors mRNA in the renal medulla of TGR rats.

5

Role of Arc phosphorylation in structural plasticity

51%

Gozdz A. , Nikolaienko O. , Urbanska M. , Cymerman I. , Sitkiewicz E. , Blazejczyk M. , Dadlez M. , Bramham C. , Jaworski J.

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nr Suppl.1

EN

Arc protein was shown to control synaptic AMPA receptor content, dendritic spine maintenance, and structure. Given its importance for neuronal function, Arc protein expression has to be tightly regulated and it occurs via ubiquitination and proteasomal degradation. Glycogen synthase kinases α and β (GSK3α/β) are serine‑threonine kinases abundantly expressed in neuronal cells, crucial for neuronal plasticity. GSK3α/β phosphorylate and prime numerous proteins for ubiquitination and degradation, however until now no interaction between Arc and GSK3α/β has been reported. The present study aims to address if and how GSK3α/β affects Arc protein expression, and whether their interaction plays a role in the regulation of dendritic spine morphology. GSK3-dependent Arc protein degradation and the effects of this process on dendritic spine morphology were studied in cultured embryonic cortical and hippocampal murine neurons upon NMDA receptors stimulation. Arc protein residues modified in GSK3‑dependent manner were identified by mass spectrometry. Obtained results were confirmed by in vitro kinase assays and the use of anti‑phospho‑Arc antibodies. We observed higher Arc levels in neurons exposed to NMDA upon GSK3α/β inhibition. In vitro kinase assays revealed that Arc is a substrate for GSK3α and β. Further analysis identified four residues phosphorylated by GSK3α/β (S170, T175, T368, T380) and one ubiquitinated in GSK3‑dependent manner (K136). Finally, we demonstrated that quadruple phosphodeficient mutant of Arc, as well as ubiquitination‑resistant Arc, were more stable in neurons upon NMDAR stimulation, and produced significant thinning of dendritic spine head. Our results identify GSK3α/β‑catalyzed Arc phosphorylation and degradation as a novel mechanism for controlling the duration of Arc expression and its effect on dendritic spine structure.