76 research outputs found
A protein kináz C szerepe a sejtszóródás szabályozásában = Role of protein kinase C in the control of cell scattering
CĂ©lunk annak felderĂtĂ©se volt, hogy a protein kináz C a HGF jelpályában milyen mechanizmus segĂtsĂ©gĂ©vel kĂ©pes gátolni a foszfatidilinozitol 3-kináz aktivitását. MegállapĂtottuk, hogy a PKCalfa (de a PKCepszilon nem), foszforilálja a p110alfa/p85 PI 3-kináz katalitikus alegysĂ©gĂ©t Ă©s ezzel csökkenti a PI 3-kináz katalitikus aktivitását. A HepG2 sejtek HGF-fel indukált szĂłrĂłdása során ez a folyamat lehet felelĹ‘s a PI 3-kináz aktiválĂłdás idĹ‘tartamának csökkentĂ©sĂ©Ă©rt Ă©s Ăgy a PI 3-kináz-dependens migráciĂł negatĂv szabályozásáért. A HepG2 sejtek forbol Ă©szter hatására törtĂ©nĹ‘ migráciĂłja viszont nem a PI 3-kináz-dependens, Rac aktiválást igĂ©nylĹ‘ jelpálya segĂtsĂ©gĂ©vel indukálĂłdik, hanem egy alternatĂv mechanizmussal. Ezt jellemzi a cortactin intenzĂv transzlokáciĂłja a plazmamembránhoz, amely jelensĂ©g HGF hatására nem figyelhetĹ‘ meg. In vitro kĂsĂ©rletekben a PKC foszforilálta a p110bĂ©ta/p85 PI 3-kináz katalitikus alegysĂ©gĂ©t is, de ez a foszforiláciĂł nem csökkentette a PI 3-kináz katalitikus aktivitását. MegállapĂtottuk, hogy a p110bĂ©ta/p85 PI 3-kináz katalitikus alegysĂ©gĂ©nek foszforiláciĂłja vĂ©gbemegy a HepG2 sejtekben is. Ezt a hepatoma sejtekre specifikusnak látszĂł foszforiláciĂłt azonban, sejten belĂĽl nem a PKC vĂ©gzi, hanem cAMP hatására stimulálĂłdik. FeltĂ©telezhetĹ‘, hogy ez a folyamat a májban, az inzulin jelpálya negatĂv szabályozásában játszik szerepet. Ennek bizonyĂtására mĂ©g folytatĂłdnak a kĂsĂ©rletek. | Our aim was to reveal the mechanism used by protein kinase C to inhibit the activity of phosphatidylinositol 3-kinase in the signalling system of HGF. We found that PKC?alpha(but not PKCepsilon) decreased the catalytic activity of the p110alpha/p85 PI 3-kinase by the phosphorylation of the catalytic subunit. This process can decrease the duration of the HGF-induced PI 3-kinase activation in HepG2 cells and in this way it can be responsible for the negative regulation of the migration. Contrarily, the phorbol ester-stimulated migration of HepG2 cells was found to be due to a Rac-independent mechanism and did not require the activation of PI 3-kinase. This alternative mechanism was characterised by the intensive translocation of cortactin to the plasma membrane, which was not detectable in HGF-induced cells. In vitro PKC was able to phosphorylate the catalytic subunit of the p110beta/p85 PI 3-kinase, as well, but this did not decrease the catalytic activity of PI 3-kinase. Nevertheless, we found that the phosphorylation of the catalytic subunit of the p110beta/p85 PI 3-kinase occurred in HepG2 cells. However, the intracellular phosphorylation of the catalytic subunit of p110?/p85 PI 3-kinase was not catalysed by PKC but was stimulated by cAMP and seemed to be a cell-specific process. It is conceivable that this phosphorylation plays some role in the negative regulation of the insulin signalling in the liver. This presumption requires further investigations
Complex formation of EphB1/Nck/Caskin1 leads to tyrosine phosphorylation and structural changes of the Caskin1 SH3 domain.
Scaffold proteins have an important role in the regulation of signal propagation. These proteins do
not possess any enzymatic activity but can contribute to the formation of multiprotein complexes. Although
scaffold proteins are present in all cell types, the nervous system contains them in the largest amount. Caskin
proteins are typically present in neuronal cells, particularly, in the synapses. However, the signaling mechanisms by which Caskin proteins are regulated are largely unknown.
Here we demonstrate that EphB1 receptor tyrosine kinase can recruit Caskin1 through the adaptor protein
Nck. Upon activation of the receptor kinase, the SH2 domain of Nck binds to one of its tyrosine residues, while Nck
SH3 domains interact with the proline-rich domain of Caskin1. Complex formation of the receptor, adaptor and
scaffold proteins results in the tyrosine phosphorylation of Caskin1 on its SH3 domain. The phosphorylation sites
were identified by mass-spectrometry as tyrosines 296 and 336. To reveal the structural consequence of this
phosphorylation, CD spectroscopy was performed. This measurement suggests that upon tyrosine phosphorylation
the structure of the Caskin1 SH3 domain changes significantly.
Taken together, we propose that the scaffold protein Caskin1 can form a complex with the EphB1
tyrosine kinase via the Nck protein as a linker. Complex formation results in tyrosine phosphorylation of the Caskin1
SH3 domain. Although we were not able to identify any physiological partner of the SH3 domain so far, we could
demonstrate that phosphorylation on conserved tyrosine residues results in marked changes in the structure of the
SH3 domain
Az akut pancreatitis pathomechanizmusának és terápiájának a vizsgálata = Pathomechanism and therapy of acute pancreatitis
Choleszterin gazdag diĂ©tával kiváltott hyperlipidemia nem befolyásolta az enyhe, ödĂ©más pancreatitist, de sĂşlyosbĂtotta a nekrotizálĂł pancreatitist. Hyperlipidemia csökkentette az endogĂ©n gyökfogĂłk Ă©s a cNOS szintjĂ©t, iNOS Ă©s NF-kB aktiváciĂłt idĂ©zett elĹ‘ Ă©s fokozta az ONOO- kĂ©pzĹ‘dĂ©st a pancreasban. Ezen eltĂ©rĂ©sek lehetnek felelĹ‘sek a nekrotizálĂł pancreatitis sĂşlyosbodásáért. Akut pancreatitis esetĂ©n az enterális táplálás az állatok sĂşlyvesztĂ©sĂ©t, a mortalitást, a pancreatitis sĂşlyosságát Ă©s a pancreas bakteriális felĂĽlfertĹ‘zĹ‘dĂ©sĂ©t mĂ©rsĂ©kelte, a pancreas regeneráciĂłját gyorsĂtotta. Ezen hatásokĂ©rt a bĂ©lbe jutĂł táplálĂ©k trophicus hatása Ă©s a bĂ©lnyálkahártya integritásáért felelĹ‘s nitrogĂ©n oxid anyagcserĂ©ben bekövetkezĹ‘ kedvezĹ‘ változások tehetĹ‘k felelĹ‘ssĂ©. A biopsziás mintavĂ©tel nem teljesen megbĂzhatĂł a sessilis nyálkahártya lĂ©ziĂłk azonosĂtásában. EzĂ©rt egy adott lĂ©ziĂłnál, a mĂ©retĂ©tĹ‘l Ă©s a tĂpusátĂłl fĂĽggĹ‘en a teljes, endoszkĂłpos eltávolĂtásra kell törekedni, hogy biztos diagnĂłzist lehessen felállĂtani, ill. Ăgy egyben vĂ©gleges terápiát is lehet nyĂşjtani. Szteroid terápia klinikai, morfolĂłgiai Ă©s funkcionális regressziĂłt eredmĂ©nyez autoimmun pancreatitisben. Az MR kĂ©palkotás a morfolĂłgiai Ă©s a funkcionális változásokat egyaránt kĂ©pes detektálni a hasnyálmirigyben. Ez növeli a vizsgálĂłmĂłdszer diagnosztikus hatĂ©konyságát a krĂłnikus pancreatitis korai felismerĂ©sĂ©ben. | Hyperlipidemia induced with cholesterol-enriched diet did not worsen edematous, but aggravated necrotizing pancreatitis. Hyperlipidemia leads to decreases in endogenous scavenger and cNOS activities, results in iNOS and NF-?B activation and stimulates ONOO- generation in the pancreas, which may be responsible for the aggravation of acute necrotizing pancreatitis. Enteral feeding reduces the weight loss, mortality, the severity of acute pancreatitis, and the bacterial superinfection of pancreas, fasten the regeneration of pancreas in experimental acute pancreatitis. The trophic effects of nutriments in the gut, and the favorable modification in nitric oxide metabolism are responsible for these changes. Forceps biopsy is insufficiently reliable for the identification of gastric polyps. These lesions should be fully resected by endoscopic mucosal resection for a final diagnosis and (depending on the lesion size and type) possibly definitive treatment. Steroid therapy is clinically, morphologically, and functionally effective in patients with autoimmun pancreatitis. MRCP permits visualization of the ductal changes and furnishes functional information on the pancreas; this combination may enhance its diagnostic accuracy so that MRCP can become a valuable diagnostic means in early-stage chronic pancreatitis
Terápiás cĂ©lpontok acut pancreatitisben: KĂsĂ©rletes Ă©s klinikai vizsgálatok = Therapeutic targets in acute pancreatitis: Experimental and clinical studies
1. Vizsgálataink fontos eredmĂ©nye egy Ăşj, jĂłl standardizálhatĂł kĂsĂ©rletes akut pancreatitis modell kifejlesztĂ©se. Az arginin metabolitok vizsgálata során azt találtuk, hogy l-ornitinnel pancreas elhalással járĂł pancreatitis válthatĂł ki patkányokban. A modell lehetĹ‘sĂ©get ad a kĂłrfolyamatok tanulmányozása mellett a preventĂv hatásĂş szerek kĂsĂ©rletes tesztelĂ©sĂ©re is. 2. MegállapĂtottuk, hogy a nekrĂłzissal járĂł formákban Ă©szlelhetĹ‘ gyulladásos mediátorok szabályozásában az NF-?B transzkripiĂłs faktor központi szerepet játszik. 3. Az NF-?B aktiváciĂłját szteroid-dependens mechanizmusok is regulálják. GlĂĽkokortikoid csökkenti, szteroid receptor antagonisa fokozza az aktiváciĂłt. 4. Igazoltuk, hogy a pancreatitis szövĹ‘dmĂ©nyeinek kialakulásában a makrofág migráciĂł gátlĂł faktor (MIF), a kĂ©sĹ‘i szövĹ‘dmĂ©nyekben a high mobilty group box protein 1 (HMGB1), Ă©s szolubilis receptorának (sRAGE) központi patogenetikai szerepe van. 5. Biliáris akut pancreatitis vizsgálata során kimutattuk, hogy epesavak (pl. chenodeoxykĂłlsav) dĂłzisfĂĽggĹ‘en csökkentik a pancreas duktális bikarbonát szekrĂ©ciĂłt, ami jelentĹ‘sen befolyásolja a bilio-pancreaticus reflux elleni vĂ©delemet. 6. Fontos eredmĂ©nyĂĽnk a proteosoma inhibitorok protektĂv hatásának kimutatása kĂsĂ©rletes akut pancreatitisben. Bortezomid hatását vizsgálva azt találtuk, hogy a szer hĹ‘sokk fehĂ©rje (HSP) indukciĂłra is kĂ©pes. A bortezomid klinikai kiprĂłbálása a humán akut pancreatitis kezelĂ©sĂ©ben is elĹ‘relĂ©pĂ©st hozhat. | 1. We have developed a new and well-standardized pancreatitis model in rats. Administration of l-ornitine evoked a severe necrotizing pancreatitis. This model allows us to study the pathogenesis of acute pancreatitis and to test the protective effect of new drug candidate molecules. 2. Our studies revealed the pivotal role of the transcriptional factor NF-?B in the regulation of inflammatory processes in severe necrotizing pancreatitis. The activation of NF-kappaB is regulated by steroid dependent mechanisms. NF-?B activation is decreased in response to glucocoriticoids whereas steroid receptor antagonists increase the process. 4. We have demonstrated that the early complications of pancreatitis are mediated by macrophage migration inhibitory factor (MIF), whereas high mobilty group box protein 1 (HMGB1) and its soluble receptor (sRAGE) are responsible for the late complications of the disease. 5. In vitro studies revealed a dose-dependent inhibitory effect of different bile salts (chenodeoxycholic acid) on pancreatic ductal bicarbonate secretion. The inhibitory effect of CDCA result in a decreased protective capacity of pancreatic ducts in case of biliary reflux. 6. We have proved the protective effect of different proteosome inhibitors in experimental acute pancreatitis. Bortezomide was also demonstrated to induce heat shock proteins (HSPs). The clinical application of this candidate drug in acute pancreatitis may result new perspectives in the line of treatment options
Investigating the effect of grit trait on performance and success in Hungarian athlete’s sample
BackgroundThe aim of the present study is to translate the Grit questionnaire into Hungarian and validate specifically within the context of sports. The second goal is to assess the questionnaire in Hungarian as a pilot study in the athlete population and to compare the grit trait with the coaches’ athlete evaluation.MethodsTwo hundred and sixty nine athletes, including 40 national team players, took part in the study, with an average age of 18.17 years (SD = 5.51). For the preliminary assessment, the Cloninger Temperament and Character Questionnaire (TCI-RH) was used; the coaches’ athlete evaluation was modeled on a talent map.ResultsThe confirmatory factor analysis confirmed the fit of the two-factor structure, and the internal reliability of the questionnaire scales also proved to be adequate. 2. There is no relationship between adolescents’ perceived grit and coach ratings. 3. The national team players achieved a higher grit score.ConclusionBased on the psychometric indicators, the validity and reliability of the questionnaire proved to be adequate. Therefore, it is applicable and useful for psychological practitioners and researchers in the Hungarian population within the context of sports
Szociális intézmények értékelési lehetőségeinek vizsgálata egy idősek ápoló-gondozó otthona példáján keresztül = Examination of social institutions evaluation possibilities through the example of a nursing an care home
In some rural areas the sustainability and operation of certain social institutions have
become not only a professional, but rather a complex issue lately, from some points of
view. Currently, beside providing various services, it has become a significant challenge
to operate their infrastructures, maintain and supply the human background, and meet
different evaluation expectations. This latest may only be carried out perfectly, which
means that these organizations must meet legal requirements. In our study, we want emphasize
this topic through an instance of an organization, which became highlighted from social-political points of view and it still tries to meet the various expectations. This study also tries to reveal the different evaluation methods, which are applied when experts, political decision makers try to assess the operation of this organization. It seems obvious that evaluation results may differ and the operation may not be examined from only one point of view
Szociális intézmények értékelési lehetőségeinek vizsgálata egy idősek ápoló-gondozó otthona példáján keresztül = Examination of social institutions evaluation possibilities through the example of a nursing an care home
In some rural areas the sustainability and operation of certain social institutions have
become not only a professional, but rather a complex issue lately, from some points of
view. Currently, beside providing various services, it has become a significant challenge
to operate their infrastructures, maintain and supply the human background, and meet
different evaluation expectations. This latest may only be carried out perfectly, which
means that these organizations must meet legal requirements. In our study, we want emphasize
this topic through an instance of an organization, which became highlighted from social-political points of view and it still tries to meet the various expectations. This study also tries to reveal the different evaluation methods, which are applied when experts, political decision makers try to assess the operation of this organization. It seems obvious that evaluation results may differ and the operation may not be examined from only one point of view
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