The physiological role of electron transfer systems  Page description

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Details of project

  
Identifier
49851
Type NI
Principal investigator Spät, András
Title in Hungarian Elektron transzfer rendszerek élettani szerepe
Title in English The physiological role of electron transfer systems
Panel Physiology, Pathophysiology, Pharmacology and Endocrinology
Department or equivalent Laboratory for Neurobiochemistry (Office for Research Groups Attached to Universities and Other Institutions)
Participants Ádám, Veronika
Bánhegyi, Gábor
Chinopoulos, Christos
Csala, Miklós
Czegle, Ibolya Anett
Dóczi, Judit
Hunyady, László
Kardon, Tamás Zoltán
Koncz, Péter
Lévay, Magdolna
Ligeti, Erzsébet
Lizák, Beáta
Mandl, József
Margittai, Éva
Nagy, Gábor
Petheo, Gábor
Sipos, Arnold
Szanda, Gergő
Szekeres, Mária
Szidonya, László
Timár, Csaba István
Törőcsik, Beáta
Tretter, László
Vajda, Szilvia
Wunderlich, Lívius
Starting date 2005-01-01
Closing date 2008-06-30
Funding (in million HUF) 87.000
FTE (full time equivalent) 24.27
state closed project





 

Final report

  
Results in Hungarian
Fagocitákban leírtuk a NADPH oxidázt szabályozó két különböző GTPáz aktiváló fehérje szabályozását és a kísérő K+ transzport baktérium ölő hatását. Agyi mitokondriumokban (mito) a légzési lánc I. komplexének szubsztrátjai membránpotenciál (Em) függően reaktív oxigénszármazékot (ROS) képeznek. Az alfa-glicerofoszfát (aGP) ROS-t képez az I. komplexen és az aGP-dehidrogenáz enzimen, utóbbit a Ca2+ aktivája. Idegvégződésekben a mito ROS képzését az Em nem befolyásolja. A mito-k elektromos szincíciumot képeznek, de a Ca2+ diffúziója korlátozott. Alacsony O2.- szint a Ca2+ -mobilizáló agonista Ca2+ jel képző hatását glomerulóza sejtben gátolja. A ROS támadáspontja a belső raktárból történő Ca2+ felszabadulás. UV hatására a mito Ca2+ felvétele is csökkent. Angiotenzin II –vel ingerelt H295R sejtben a mito Ca2+ jel képzés sebessége a mito és az endoplazmás retikulum (ER) közelségével korrelál. A p38 MAPK és az újtípusú PKC izoformák egyidejű gátlása a Ca2+ jelnek a citoszolból a mito-ba történő áttevődését gátolja és a fenti korrelációt megszünteti. Az ER lumenében a tiol/diszulfid rendszertől elkülönülő NAD(P)+/NAD(P)H rendszer működik. Redox állapotát a glukóz-6-foszfát transzporter és az intraluminális oxidoreduktázok határozzák meg. A redukált állapot fenntartása szükséges a glukokortikoidok prereceptoriális aktiválásához, s egyes sejtekben antiapoptotikus hatású. Jellemeztük az ER szulfát transzporterét, valamint a transzlokon peptid csatorna anion permeabilitását.
Results in English
We described in phagocytes the regulation of two GTPase activating proteins, terminating the activity of plasmalemmal NADPH oxidase and the role of K+ movements in bacterial killing. In brain mitochondria complex I dependent substrates show a membrane potential (Em) dependent reactive oxygen species (ROS) formation. ROS production by alpha-glycerophosphate (aGP) occured at complex I and on the aGP-dehydrogenase enzyme. The latter is activited by Ca2+. Mitochondria form an electric syntitium but the diffusion of Ca2+ is limited. In glomerulosa cells, at low [O2.-] angiotensin-induced Ca2+ signalling is attenuated, the site of ROS action is Ca2+ release from the internal stores. The rate of mitochondrial Ca2+ uptake in angiotensin-stimulated cells correlates with the vicinity of the mitochondrion and the endoplasmic reticulum (ER). Simultaneous activation of p38 MAPK and the novel isoforms of PKC attenuates the transfer of cytosolic Ca2+ signal into the mitochondria and abolishes this correlation. In the ER we observed a novel NAD(P)+/NAD(P)H system different from the thiol/disulphide system. Its reduced state is tuned by the glucose-6-phosphate transporter and the luminal oxidoreductases and is required for the prereceptorial activation of glucocorticoids. We have characterized the sulphate transport in the ER, and the contribution of the translocon peptide channel to the membrane permeation of small anions.
Full text http://real.mtak.hu/2038/
Decision
Yes





 

List of publications

  
Spät A: Calcium microdomains and the fine control of cell function – An introduction, Cell Calcium 40, 403-404, 2006
Gerencser AA, Adam-Vizi V: Mitochondrial Ca2+ Dynamics Reveals Limited Intramitochondrial Ca2+ Diffusion., Biophys. J. 88 (1): 698-714., 2005
Sipos I. Torocsik B. Tretter L. Adam-Vizi V.: Impaired regulation of pH homeostasis by oxidative stress in rat brain capillary endothelial cells., Cellular & Molecular Neurobiology. 25 (1): 141-151,, 2005
Tretter L, Adam-Vizi V.:: Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress, Phil. T. Roy. Soc. B. 360 (1464): 2335-2345,, 2005
Adam-Vizi V.:: Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain sources., Antioxidants & Redox Signaling. 7 (9-10): 1140-1149, 2005
Tretter L, Liktor B, Adam-Vizi V.:: Dual effect of pyruvate in isolated nerve terminals: generation of reactive oxygen species and protection of aconitase., Neurochemical Research. 30 (10): 1331-1338, 2005
Vajda Sz, Leon C, Gachet C, Machovich R, Adam-Vizi V, Bartha K.:: PAR-4 mediates sustained calcium oscillations and ERK 1/2 phosphorylation in B10 endothelial cells from rat brain., Arteriosclerosis, Thrombosis and Vascular Biology. submitted, 2005
Sirokmany G, Szidonya L, Kaldi K, Gaborik Z, Ligeti E, Geiszt M.: Sec14 homology domain targets p50RhoGAP to endosomes and provides a link between Rab- and Rho GTPases., J Biol Chem. 2005 Dec 27; [Epub ahead of print], 2005
Staines A., Bánhegyi G., Mandl J., Coughtrie M.W.H., Burchell B., Csala M.:: Application of high-performance liquid chromatography-electrospray ionisation mass spectrometry to measure microsomal membrane transport of glucuronides., Anal. Biochem. 342, 45–52, 2005, 2005
Csala M., Senesi S., Bánhegyi G., Mandl J., Benedetti A.:: Characterization of sulfate transport in the hepatic endoplasmic reticulum., Arch. Biochem. Biophys. 440, 173-180,, 2005
Margittai É., Bánhegyi G., Nagy G., Kiss A., Mandl J., Schaff Z., Csala M.:: Scurvy leads to endoplasmic reticulum stress and apoptosis in the liver of guinea pigs., J. Nutr. 135, 2530-2534, 2005
Papp E., Nardai G., Mandl J., Bánhegyi G., Csermely P.:: FAD oxidizes the Ero1-PDI electron transfer chain. The role of membrane integrity., Biochem. Biophys. Res. Commun. 338, 938-945,, 2005
Czegle I, Piccirella S, Senesi S, Csala M, Mandl J, Bánhegyi G, Fulceri R, Benedetti A.:: Cooperativity between 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase is based on a common pyridine nucleotide pool in the lumen of the, Mol. Cell. Endocrinol. 2005 Dec 5; [Epub ahead of print], 2005
Pitter J.G., Szanda G., Duchen M.R., Spät A.:: Prostaglandin F2alfa potentiates the calcium dependent activation of mitochondrial metabolism in luteal cells, Cell Calcium 37, 35-44, 2005
Petersen O.H., Spät A., Verkhratsky A.:: Introduction: reactive oxygen species in health and disease, Phil. Trans. Royal Soc. B 360, 2197-2199,, 2005
P. Moskwa, M.-H. Paclet, M.-C. Dagher and E. Ligeti: Autoinhibition of p50 Rho GTPase-activating protein (GAP) is released by prenylated small GTPases, J. Biol. Chem. 280. 6716-6720., 2005
B.K. Rada, M. Geiszt, C. Hably and E. Ligeti: Consequences of the electrogenic function of the phagocytic NADPH oxidase, Phil. Transaction B 360. 2293-2300., 2005
T. DeCoursey and E. Ligeti: Regulation and termination of NADPH oxidase activity, Cellular and Molecular Life Sciences 62. 2173-2193., 2005
Chinopoulos C, Adam-Vizi V.:: Calcium, mitochondria and oxidative stress in neuronal pathology: novel aspects of an enduring theme, FEBS Journal 273(3), 433-450,, 2006
Tretter L, Adam-Vizi V.: Moderate dependence of ROS formation on ΔΨm in isolated brain mitochondria supported by NADH-linked substrate, Neurochem Res 2006 Aug 24; PMID: 16933091, 2006
Tretter L, Mayer-Takacs D, Adam-Vizi V.: The effect of bovine serum albumin on the membrane potential and reactive oxygen species generation in succinate-supported isolated brain mitochondria, Neurochem Int. 50(1), 139-47, 2007, 2006
Adam-Vizi V, Christos Chinopoulos: Bioenergetics and the formation of mitochondrial reactive oxygen species, Trends in Pharmacological Sciences. 27(12), 639-645,, 2006
Szidonya, L.; Süpeki, K.; Karip, E.; Turu, G.; Várnai, P.; Clark, A.J.L.; Hunyady, L.: AT1 receptor blocker-insensitive mutant AT1A angiotensin receptors reveal the presence of G protein-independent signaling in C9 cells, Biochem. Pharmacol. 73: 1582-92., 2007
Czegle I., Piccirella S., Senesi S., Csala M., Mandl J., Bánhegyi G., Fulceri R., Benedetti A.: Cooperativity between 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase is based on a common pyridine nucleotide pool in the lumen ..., Mol. Cell. Endocrinol. 248, 24-25,, 2006
Piccirella S., Czegle I., Lizák B., Margittai É., Senesi S., Papp E., Csala M., Fulceri R., Csermely P., Mandl J., Benedetti A., Bánhegyi G.: Uncoupled redox systems in the lumen of the endoplasmic reticulum: pyridine nucleotides stay reduced in an oxidative environment, J. Biol. Chem. 281, 4671-4677,, 2006
Kardon T., Nagy G., Csala M., Kiss A., Schaff Z., Literáti Nagy P., Wunderlich L., Bánhegyi G., Mandl J.: Influence of BGP-15, a nicotinic amidoxime derivative, on the vascularization and growth of murine hepatoma xenografts, Anticancer Res. 26, 1023-1028, 2006
Csala M., Bánhegyi G., Benedetti A.: Endoplasmic reticulum: A metabolic compartment. (review), FEBS Lett. 580, 2160-2165, 2006
Lizák B., Czegle I., Csala M., Benedetti A., Mandl J., Bánhegyi G: Translocon Pores in the Endoplasmic Reticulum Are Permeable to Small Anions, Am. J. Physiol. – Cell Physiol. 291, C511-517, 2006
Gamberucci A., Konta L., Colucci A., Giunti R., Magyar É.J., Mandl J., Bánhegyi G., Benedetti B., Csala M: Green tea flavonols inhibit glucosidase II., Biochem. Pharmacol. 72, 640-646, 2006
Nagy G., Kardon T., Wunderlich L., Szarka A., Kiss A., Schaff Zs., Bánhegyi G., Mandl J: Acetaminophen induces ER dependent signaling in mouse liver, Arch. Biochem. Biophys. doi:10.1016/j.abb.2006.11.021, 2006
Révész K., Tüttő A., Margittai É., Bánhegyi G., Mandl J., Csala M: Glucuronide transport across the endoplasmic reticulum membrane is inhibited by epigallocatechin gallate and other green tea polyphenols, Int. J. Biochem. Cell Biol., 2006
Turu G., Szidonya L., Gáborik Zs., Buday L., Spät A., Clark A.J.L., Hunyady L.: Differential -arrestin2 binding of AT1 and AT2 angiotensin receptors, FEBS Letters, 580, 41-45, 2006
Koncz P., Szanda G., Rajki A., Spät A: Reactive oxygen species, Ca2+ signaling and mitochondrial NAD(P)H level in adrenal glomerulosa cells, Cell Calcium 40, 347-357, 2006
Szanda G., Koncz P., Várnai P., Spät A.: Mitochondrial Ca2+ uptake with and without the formation of high-Ca2+ microdomains, Cell Calcium 40, 527-537, 2006
Bánhegyi G., Csala M., Benedetti A: Endoplasmic Reticulum: Topics in Chemical Biology, Wiley Encyclopedia of Chemical Biology (invited paper, revised version), 2006
Femling JK, Cherny VV, Morgan D, Rada B, Davis AP, Czirjak G, Enyedi P, England SK, Moreland JG, Ligeti E, Nauseef WM, DeCoursey TE.: The antibacterial activity of human neutrophils and eosinophils requires proton channels but not BK channels, J Gen Physiol. 127. 659-72., 2006
Ligeti E, Settleman J.: Regulation of RhoGAP specificity by phospholipids and prenylation, Methods Enzymol. 406. 104-17., 2006
Turu, G.; Szidonya, L.; Gáborik, Z.; Buday, L.; Spät, A.; Clark, A.J.L.; Hunyady, L.:: Differential ß-arrestin binding of AT1 and AT2 angiotensin receptors, FEBS Letters 580:41-5, 2006
B.Rada, Cs. Hably, A. Meczner, Cs. Timár, G. Lakatos, P. Enyedi, E. Ligeti: Role of Nox2 in elimination of microorganisms, Seminars in Immunopathology DOI 10.1007/s00281-008-0126-3, 2008
Spät A., Szanda G., Csordás Gy., Hajnóczky Gy: High and low calcium-dependent mechanisms of mitochondrial calcium signalling, Cell Calcium 44, 51-63, (published on-line: February 19, 2008, doi:10.1016/j.ceca.2007.11.015), 2008
Szanda G., Koncz P., Rajki A., Spät A: Participation of p38 MAPK and a novel-type protein kinase C in the control of mitochondrial Ca2+ uptake, Cell Calcium 43, 250-259, (published on-line: doi:10.1016/j.ceca.2007.05.013), 2008
Turu, G.; Szidonya, L.; Gáborik, Z.; Buday, L.; Spät, A.; Clark, A.J.L.; Hunyady, L.:: Differential ß-arrestin binding of AT1 and AT2 angiotensin receptors, FEBS Letters 580:41-5, 2006
Szanda G., Rajki A., Gallego-Sandín S., Garcia-Sancho J., Spät A.: Effect of cytosolic Mg2+ on mitochondrial Ca2+ signalling, Pflügers Archiv, in press (DOI: 10.1007/s00424-008-0551-0), 2008
Komary Z, Tretter L, Adam-Vizi V: H(2)O(2) generation is decreased by calcium in isolated brain mitochondria, Biochim Biophys Acta 1777: 800-807., 2008
Gerencser AA, Doczi J, Torocsik B, Bossy-Wetzel E, Adam-Vizi V: Mitochondrial swelling measurement in situ by optimized spatial filtering: astrocyte-neuron differences, Biophys J. Epub ahead of print, 2008
Vajda S, Bartha K, Wilhelm I, Krizbai IA, Adam-Vizi V: Identification of protease-activated receptor-4 (PAR-4) in puromycin-purified brain capillary endothelial cells cultured on Matrigel, Neurochem Int 52: 1234-1239., 2008
Tretter L, Adam-Vizi V: Uncoupling is without an effect on the production of reactive oxygen species by in situ synaptic mitochondria, J Neurochem 103: 1864-1871., 2007
Tretter L, Takacs K, Kover K, Adam-Vizi V: Stimulation of H(2)O(2) generation by calcium in brain mitochondria respiring on alpha-glycerophosphate, J Neurosci Res 85: 3471-3479., 2007
Tretter L, Takacs K, Hegedus V, Adam-Vizi V: ) Characteristics of alpha-glycerophosphate-evoked H2O2 generation in brain mitochondria, J Neurochem 100: 650-663., 2007
Tretter L, Mayer-Takacs D, Adam-Vizi V: The effect of bovine serum albumin on the membrane potential and reactive oxygen species generation in succinate-supported isolated brain mitochondria, Neurochem Int 50: 139-147., 2007
Tretter L, Adam-Vizi V: Moderate dependence of ROS formation on DeltaPsim in isolated brain mitochondria supported by NADH-linked substrates., Neurochem Res 32: 569-575., 2007
Kardon T, Senesi S, Marcolongo P, Legeza B, Bánhegyi G, Mandl J, Fulceri R, Benedetti A.: Maintenance of luminal NADPH in the endoplasmic reticulum promotes the survival of human granulocytes, FEBS Lett. 582(13):1809-15., 2008
Lizák B, Csala M, Benedetti A, Bánhegyi G.: The translocon and the non-specific transport of small molecules in the endoplasmic reticulum (Review), Mol Membr Biol 25(2):95-101., 2008
Margittai E, Bánhegyi G.: Isocitrate dehydrogenase: A NADPH-generating enzyme in the lumen of the endoplasmic reticulum, Arch Biochem Biophys 471:184-90., 2008
Bánhegyi G, Benedetti A, Csala M, Mandl J.: Stress on redox, FEBS Lett. 581(19)3634-40. Review, 2007
Csala M, Marcolongo P, Lizák B, Senesi S, Margittai E, Fulceri R, Magyar JE, Benedetti A, Bánhegyi G.: Transport and transporters in the endoplasmic retiuculum, Biochin Biophys Acta 1768(6)1325-41. Review, 2007
Csala M, Margittai E, Senesi S, Gamberucci A, Bánhegyi G, Mandl J, Benedetti A.: Inhibition of hepatic glucose 6-phosphatase system by the green tea flavanol epigallocatechin gallate, FEBS Lett. 581(8):1693-8., 2007



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