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Mechanika osrodkow komorkowych i granularnych

100%

Gozdz A.

Acta Agrophysica

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1999

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tom 24

57-65

W pracy przedstawiono zarysy metody jednolitego opisu ośrodków granularnych i komórkowych. Formalizm wykorzystuje elementy mechaniki kwantowej chociaż można go zakwalifikować do metod mikroskopowo-makroskopowych, Pozwala on modelować własności ośrodka bazując na znajomości fenomenologicznych oddziaływań pomiędzy jego granulami lub komórkami.

2

FK506 prevents pro-inß ammatory and cytotoxic activation of cytokine-stimulated rat astrocytes

63%

Gozdz A., Kaminska B.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 1

Reactive astrogliosis is implicated in many acute and chronic neuropathological conditions and involves astrocyte proliferation, activation and hypertrophy accompanied by production of cytokines, growth factors and metabolic alterations. Astrocyte activation may exert both benefi cial and detrimental effects on nervous system cells, therefore its modulation is an attractive target for neuroprotective therapies. We have demonstrated that a widely used immunosuppressant and calcineurin inhibitior FK506 potently reduced gliosis in vivo and improved recovery in a rat stroke model (Zawadzka and Kaminska 2004, Glia 49: 36ñ51). To dissect the mechanism of FK506 action on activated astrocytes, we employed a model of ìreactive astrogliosis in vitroî based on primary rat astrocyte cultures stimulated with the mixture of pro-infl ammatory cytokines: IL1-beta, IFN-gamma and TNF-alpha. Cytokine cocktail induced activation of NFkappaB, p38 MAPK and JNK signaling pathways followed by cellular hypertrophy, rearrangement of astrocyte cytoskeleton, nitric oxide production and expression of mRNA for IL-6 and trail. FK506, as well as another calcineurin inhibitor cyclosporin A, reduced the astrocyte hypertrophy. FK506 decreased the level of activated p38 MAPK, as well as down-regulated trail mRNA. Interestingly, FK506 was also able to reduce the activation of p38 MAPK in astrocytes exposed to hydrogen peroxide implicating potential of this drug in counteracting some effects of oxidative stress observed during ischemic reperfusion or neuroinfl ammation. Our data suggest that FK506 may exert its neuroprotective effect partially via inhibition of the pro-infl ammatory astroglia activation and implicate a calcineurin as a new candidate for triggering of astrogliosis. Supported by PBZ/MEiN/01/2006/32 (AG)

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

63%

Gozdz A., Pietrow M.

International Agrophysics

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1999

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tom 13

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nr 2

4

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

63%

Pietrow M., Gozdz A.

International Agrophysics

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2000

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tom 14

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nr 1

5

Extracellular signal-regulated kinase 1-2 is defense mechanism for neutrons exposed to DNA-damage

51%

Gozdz A., Chlystun M., Hetman M.

Cellular and Molecular Biology Letters

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2001

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tom 06

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nr 2B

491

6

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

51%

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

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

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.

7

Kainic acid causes mTOR activation and translocation from cytosol to the nucleus – Live imaging study

45%

Macias M., Janusz-Kaminska A., Tarkowski B., Gozdz A., Jaworski J.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

INTRODUCTION: The mechanistic target of rapamycin (mTOR) is a protein kinase, which integrates eukaryotic cell growth, metabolism and external stimuli. Most research link mTOR with control of protein translation but recent studies revealed additional mTOR function in cell nucleus. Previously, we showed that phosphorylation of mTOR (Ser2448; P-mTOR) is upregulated in neuronal nucleus upon kainate (KA) induced status epilepticus. Whether other stimuli have the same effect on nuclear mTOR phosphorylation and if increased nuclear import of mTOR contributes to this phenomenon remained unknown. Also it was not known if nuclear transport of other proteins affects mTOR signaling. AIM(S): To analyze effects of neuronal activity on nuclear translocation of mTOR and its nuclear activity. To analyze importance of nuclear transport for mTOR signaling. METHOD(S): Cultured hippocampal neurons were treated with: KA, BDNF; NMDA and chemical LTP (cLTP) protocol or TTX. mTOR activity was measured with FRET method. mTOR nuclear translocation was assessed using FRAP. Nuclear import was blocked with importazole. Immunofluorescence of P-S6 protein was used as a marker of mTOR activity. RESULTS: We found that KA, BDNF, NMDA and cLTP caused nuclear upregulation of P-mTOR. However, TTX or cLTD had no effect. FRAP and FRET revealed that mTOR activity due to KA treatment is first observed in cytosol and then in nucleus, where mTOR is translocated upon treatment. Blocking nuclear import silenced mTOR activity in response to KA and inhibited P-mTOR upregulation in the nucleus. CONCLUSIONS: Our experiments showed that increased neuronal activity upregulates nuclear P-mTOR and increases nuclear activity of mTOR due to nuclear translocation of the kinase. FINANCIAL SUPPORT: The research was supported by PNSC grants no. 2012/05/B/NZ3/00429 and 2012/07/E/ NZ3/00503.

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

45%

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

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 3

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.

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Role of Arc phosphorylation in structural plasticity

33%

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

Acta Neurobiologiae Experimentalis

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2019

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tom 79

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nr Suppl.1

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.

Ograniczanie wyników

Mechanika osrodkow komorkowych i granularnych

FK506 prevents pro-inß ammatory and cytotoxic activation of cytokine-stimulated rat astrocytes

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

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

Extracellular signal-regulated kinase 1-2 is defense mechanism for neutrons exposed to DNA-damage

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

Kainic acid causes mTOR activation and translocation from cytosol to the nucleus – Live imaging study

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

Role of Arc phosphorylation in structural plasticity