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Christoph Richter - One of the best experts on this subject based on the ideXlab platform.
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peroxynitrite stimulates the Pyridine nucleotide linked ca2 release from intact rat liver mitochondria
Biochemistry, 1996Co-Authors: Matthias Schweizer, Christoph RichterAbstract:: Rat liver mitochondria contain a specific Ca2+ release pathway which operates when oxidized mitochondrial Pyridine Nucleotides are hydrolyzed in a Ca2+-dependent manner to ADP-ribose and nicotinamide. We have previously shown that NAD+ hydrolysis is inhibited by cyclosporin A and is possible only when some vicinal thiols are cross-linked. Here we report that the thiol oxidant peroxynitrite (ONOO-), which can form from nitric oxide (nitrogen monoxide, NO.) and superoxide anion (O2-), at low concentrations stimulates the specific Ca2+ release pathway. Both peroxynitrite-induced Pyridine nucleotide hydrolysis and Ca2+ release are inhibited by cyclosporin A, and peroxynitrite is ineffective when Pyridine Nucleotides are kept reduced. Ca2+ release induced by peroxynitrite occurs with maintenance of the mitochondrial membrane potential and is not accompanied by entry of sucrose into mitochondria. The results suggest that peroxynitrite stimulates the specific Ca2+ release from intact mitochondria by modifying critical mitochondrial thiols other than glutathione in such a way that hydrolysis of oxidized Pyridine Nucleotides is achieved. These findings provide further insight into the regulation of Ca2+ release from mitochondria by nitric oxide and its congeners.
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phenylarsine oxide stimulates Pyridine nucleotide linked ca2 release from rat liver mitochondria
Biochemical Pharmacology, 1994Co-Authors: Matthias Schweizer, Peter Durrer, Christoph RichterAbstract:Abstract Rat liver mitochondria contain a specific Ca 2+ release pathway which operates when oxidized mitochondrial Pyridine Nucleotides are hydrolysed to ADPribose and nicotinamide. Here we report that the hydrophobic bifunctional thiol reagent phenylarsine oxide (PhAsO) at low concentrations stimulates this pathway by promoting a Ca 2+ -dependent hydrolysis of oxidized mitochondrial Pyridine Nucleotides. Ca 2+ release is inhibited by cyclosporine A or m -iodobenzylguanidine, compounds known to prevent intramitochondrial Pyridine nucleotide hydrolysis or protein mono(ADPribosyl)ation, respectively. At higher concentrations, PhAsO causes non-specific leakiness of mitochondria.
Gabor Banhegyi - One of the best experts on this subject based on the ideXlab platform.
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Research Article Depletion of Luminal Pyridine Nucleotides in the Endoplasmic Reticulum Activates Autophagy with the Involvement of mTOR Pathway
2016Co-Authors: Orsolya Kapuy, Gabor BanhegyiAbstract:Copyright © 2013 O. Kapuy and G. Bánhegyi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. It has been recently shown that redox imbalance of luminal Pyridine Nucleotides in the endoplasmic reticulum (ER) together with oxidative stress results in the activation of autophagy. In the present study we demonstrated that decrease of luminal NADPH/NADP+ ratio alone by metyrapone was sufficient to promote the mechanism of “self-eating ” detected by the activation of LC3. Depletion of luminal NADPH had also significant effect on the key proteins of mTOR pathway, which got inactivated by dephosphorylation. These findings were also confirmed by silencing the proteins (glucose-6-phosphate transporter and hexose-6-phosphate dehydrogenase) responsible for NADPH generation in the ER lumen. However, silencing the key components and addition of metyrapone had different effects on downstream substrates 4EBP1 and p70S6K of mTOR. The applied treatments did not compromise the viability of the cells. Our data suggest that ER stress caused by luminal NADPH depletion activates a pro-survival autophagic mechanism firmly coupled to the activation of mTOR pathway. 1
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depletion of luminal Pyridine Nucleotides in the endoplasmic reticulum activates autophagy with the involvement of mtor pathway
BioMed Research International, 2013Co-Authors: Gabor Banhegyi, Orsolya KapuyAbstract:It has been recently shown that redox imbalance of luminal Pyridine Nucleotides in the endoplasmic reticulum (ER) together with oxidative stress results in the activation of autophagy. In the present study we demonstrated that decrease of luminal NADPH/NADP+ ratio alone by metyrapone was sufficient to promote the mechanism of “self-eating” detected by the activation of LC3. Depletion of luminal NADPH had also significant effect on the key proteins of mTOR pathway, which got inactivated by dephosphorylation. These findings were also confirmed by silencing the proteins (glucose-6-phosphate transporter and hexose-6-phosphate dehydrogenase) responsible for NADPH generation in the ER lumen. However, silencing the key components and addition of metyrapone had different effects on downstream substrates 4EBP1 and p70S6K of mTOR. The applied treatments did not compromise the viability of the cells. Our data suggest that ER stress caused by luminal NADPH depletion activates a pro-survival autophagic mechanism firmly coupled to the activation of mTOR pathway.
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decreased prereceptorial glucocorticoid activating capacity in starvation due to an oxidative shift of Pyridine Nucleotides in the endoplasmic reticulum
FEBS Letters, 2010Co-Authors: Miklos Csala, Eva Kereszturi, Fanni S Kalman, Tamas Kardon, Gabor BanhegyiAbstract:Redox state of Pyridine Nucleotides of the endoplasmic reticulum (ER) lumen was determined in different nutritional conditions. NADPH-dependent cortisone reduction and NADP+-dependent cortisol oxidation were measured in rat liver microsomes, by utilizing the luminal 11β-hydroxysteroid dehydrogenase type 1 activity. Cortisone reduction decreased, while cortisol oxidation increased during onward starvation, showing that the luminal NADPH/NADP+ ratio was substantially decreased. Cortisone or metyrapone addition caused a smaller decrease in NADPH fluorescence in microsomes from starved rats. The results demonstrate that nutrient supply is mirrored by the redox state of ER luminal Pyridine Nucleotides.
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altered redox state of luminal Pyridine Nucleotides facilitates the sensitivity towards oxidative injury and leads to endoplasmic reticulum stress dependent autophagy in hepg2 cells
The International Journal of Biochemistry & Cell Biology, 2010Co-Authors: Gabor Banhegyi, Peter Szaraz, Angelo BenedettiAbstract:Maintenance of the reduced state of luminal Pyridine Nucleotides in the endoplasmic reticulum - an important pro-survival factor in the cell - is ensured by the concerted action of glucose-6-phosphate transporter and hexose-6-phosphate dehydrogenase. The mechanism by which the redox imbalance leads to cell death was investigated in HepG2 cells. The chemical inhibition of the glucose-6-phosphate transporter, the silencing of hexose-6-phosphate dehydrogenase and/or the glucose-6-phosphate transporter, or the oxidation of luminal NADPH by themselves did not cause a significant loss of cell viability. However, these treatments caused ER calcium store depletion. If these treatments were supplemented with the administration of a subliminal dose of the oxidizing agent menadione, endoplasmic reticulum vacuolization and a loss of viability were observed. Combined treatments resulted in the activation of ATF6 and procaspase-4, and in the induction of Grp78 and CHOP. In spite of the presence of UPR markers and proapoptotic signaling the effector caspases - caspase-3 and caspase-7 - were not active. On the other hand, an elevation of the autophagy marker LC3B was observed. Immunohistochemistry revealed a punctuated distribution of LC3B II, coinciding with the vacuolization of the endoplasmic reticulum. The results suggest that altered redox state of endoplasmic reticulum luminal Pyridine Nucleotides sensitizes the cell to autophagy.
Peter Ruoff - One of the best experts on this subject based on the ideXlab platform.
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Printed in d.S.A. Hysteretic Behavior of Nitrate Reductase EVIDENCE OF AN ALLOSTERIC BINDING SITE FOR REDUCED Pyridine Nucleotides*
2015Co-Authors: Cathrine Lillo, Peter RuoffAbstract:NADH:nitrate reductase undergoes an approximately 60 % reduction of its initial activity during 2 h. With the increase of inactivation, the NADH and nitrite concentration time curves become typical “sigmoidal,” i.e. the reaction velocity of the nitrate reductase cata-lyzed reaction goes through a maximum before equilib-rium is reached. About 80 % of the original activity of nitrate reductase is restored when the enzyme is incu-bated for 2 min with 200 PM NADH or NADPH. Also other NADH substrate analogues have similar effects in restoring the lost activity. After incubation with the reduced Pyridine Nucleotides, the sigmoidal appear-ance of the NADH concentration time curve disappears almost completely. Despite the fact that NADPH in-creases the activity of the enzyme, NADPH does not show any competition with the NADH-binding site of nitrate reductase and does not produce nitrite in the absence of NADH. It is therefore concluded that there must be an additional allosteric site which binds either NADH or NADPH, or other Pyridine Nucleotides with the effect of increasing the activity of the enzyme. A kinetic model is presented which simulates the ob-served experimental findings. NADH:nitrate reductase catalyzes the reduction of nitrate to nitrite. NADH + H ’ + NOT __+ NAD+ + NO; + H,O (Rl) NR Process R1 is the rate-limiting step in the assimilation of nitrate to organically bound nitrogen in higher plants and algae. NADH:nitrate reductase is a complex enzyme consist-ing of two identical monomers. Each monomer has three functional domains containing FAD, heme, and molybdenum pterin as prostetic redox groups (Caboche and Rouzir, 1990). NADH:nitrate reductase is regulated at the nucleic acid level (Caboche and Rouz6, 1990). However, fine tuning of the enzyme’s activity at the protein level may also be of physio-logical importance (Solomonson and Barber, 1990; Lillo
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hysteretic behavior of nitrate reductase evidence of an allosteric binding site for reduced Pyridine Nucleotides
Journal of Biological Chemistry, 1992Co-Authors: Cathrine Lillo, Peter RuoffAbstract:Abstract In the absence of NADH, at 25 degrees C, partially purified NADH:nitrate reductase undergoes an approximately 50% reduction of its initial activity during 2 h. With the increase of inactivation, the NADH and nitrite concentration time curves become typical "sigmoidal," i.e. the reaction velocity of the nitrate reductase catalyzed reaction goes through a maximum before equilibrium is reached. About 80% of the original activity of nitrate reductase is restored when the enzyme is incubated for 2 min with 200 microM NADH or NADPH. Also other NADH substrate analogues have similar effects in restoring the lost activity. After incubation with the reduced Pyridine Nucleotides, the sigmoidal appearance of the NADH concentration time curve disappears almost completely. Despite the fact that NADPH increases the activity of the enzyme, NADPH does not show any competition with the NADH-binding site of nitrate reductase and does not produce nitrite in the absence of NADH. It is therefore concluded that there must be an additional allosteric site which binds either NADH or NADPH, or other Pyridine Nucleotides with the effect of increasing the activity of the enzyme. A kinetic model is presented which simulates the observed experimental findings.
Andras Spat - One of the best experts on this subject based on the ideXlab platform.
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the effect of cytoplasmic ca2 signal on the redox state of mitochondrial Pyridine Nucleotides
Molecular and Cellular Endocrinology, 2004Co-Authors: Andras Spat, Janos G PitterAbstract:Abstract As first observed in rat adrenal glomerulosa cells, cytoplasmic Ca2+ signal, induced by K+, angiotensin II or vasopressin, evokes an increase in the level of reduced mitochondrial Pyridine Nucleotides, NADH and NADPH. Prostaglandin F2α and extracellular ATP exert similar effects in rat ovarian luteal cells. This coupling of cytoplasmic Ca2+ concentration and mitochondrial metabolism occurs also when the stimuli are applied at physiological concentration and under conditions when no formation of high-Ca2+ perimitochondrial microdomains may be presumed. We present evidence that low submicromolar Ca2+ signals in the cytoplasm can increase mitochondrial Ca2+ concentration and activate mitochondrial dehydrogenation processes. Several observations support the assumption that intramitochondrial Ca2+ signals play a significant role in the stimulation of steroid hormone production.
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cytoplasmic ca2 signalling and reduction of mitochondrial Pyridine Nucleotides in adrenal glomerulosa cells in response to k angiotensin ii and vasopressin
Biochemical Journal, 1997Co-Authors: Andras Spat, Tibor Rohacs, Gyorgy NagyAbstract:We have examined the mitochondrial formation of NAD(P)H in rat adrenal glomerulosa cells. A short-term elevation of the K+ concentration from 3.6 to 8.4 mM induced a reversible increase in the formation of reduced Pyridine Nucleotides. Potassium applied after the addition of rotenone had no further effect, confirming that the redox signal was of mitochondrial origin. Inhibition of aldosterone synthesis by aminoglutethimide in K+-stimulated cells decreased the rate of decay of the NAD(P)H signal upon the termination of stimulation, indicating that the NADPH formed was consumed in aldosterone synthesis. When the NAD(P)H signal was measured simultaneously with the cytoplasmic free Ca2+ concentration ([Ca2+]i), elevation of the K+ concentration to 6.6 or 8.4 mM induced parallel increases in [Ca2+]i and NAD(P)H formation. The rates of increase and decrease of NAD(P)H were lower than for [Ca2+]i, confirming that the redox signal was secondary to the Ca2+ signal. Angiotensin II (100 pM-1 nM) induced an oscillatory NAD(P)H signal which usually returned to a lower baseline concentration, while a sustained signal with superimposed oscillations was observed at higher concentrations. Simultaneous measurements showed that NAD(P)H levels followed the [Ca2+]i pattern evoked by angiotensin II. Vasopressin (100 nM) also induced parallel oscillations of [Ca2+]i and NAD(P)H. A sustained rise in the extramitochondrial Ca2+ concentration to 1 microM induced a sustained elevation of the intramitochondrial Ca2+ concentration in permeabilized cells, as measured with rhod-2. A sustained rise in [Ca2+]i evoked by long-term stimulation with 8.4 mM K+ or 2.5 nM angiotensin II resulted in sustained NAD(P)H production. These Ca2+-dependent changes in the mitochondrial redox state support the biological response, i.e. aldosterone secretion by glomerulosa cells.
Matthias Schweizer - One of the best experts on this subject based on the ideXlab platform.
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peroxynitrite stimulates the Pyridine nucleotide linked ca2 release from intact rat liver mitochondria
Biochemistry, 1996Co-Authors: Matthias Schweizer, Christoph RichterAbstract:: Rat liver mitochondria contain a specific Ca2+ release pathway which operates when oxidized mitochondrial Pyridine Nucleotides are hydrolyzed in a Ca2+-dependent manner to ADP-ribose and nicotinamide. We have previously shown that NAD+ hydrolysis is inhibited by cyclosporin A and is possible only when some vicinal thiols are cross-linked. Here we report that the thiol oxidant peroxynitrite (ONOO-), which can form from nitric oxide (nitrogen monoxide, NO.) and superoxide anion (O2-), at low concentrations stimulates the specific Ca2+ release pathway. Both peroxynitrite-induced Pyridine nucleotide hydrolysis and Ca2+ release are inhibited by cyclosporin A, and peroxynitrite is ineffective when Pyridine Nucleotides are kept reduced. Ca2+ release induced by peroxynitrite occurs with maintenance of the mitochondrial membrane potential and is not accompanied by entry of sucrose into mitochondria. The results suggest that peroxynitrite stimulates the specific Ca2+ release from intact mitochondria by modifying critical mitochondrial thiols other than glutathione in such a way that hydrolysis of oxidized Pyridine Nucleotides is achieved. These findings provide further insight into the regulation of Ca2+ release from mitochondria by nitric oxide and its congeners.
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phenylarsine oxide stimulates Pyridine nucleotide linked ca2 release from rat liver mitochondria
Biochemical Pharmacology, 1994Co-Authors: Matthias Schweizer, Peter Durrer, Christoph RichterAbstract:Abstract Rat liver mitochondria contain a specific Ca 2+ release pathway which operates when oxidized mitochondrial Pyridine Nucleotides are hydrolysed to ADPribose and nicotinamide. Here we report that the hydrophobic bifunctional thiol reagent phenylarsine oxide (PhAsO) at low concentrations stimulates this pathway by promoting a Ca 2+ -dependent hydrolysis of oxidized mitochondrial Pyridine Nucleotides. Ca 2+ release is inhibited by cyclosporine A or m -iodobenzylguanidine, compounds known to prevent intramitochondrial Pyridine nucleotide hydrolysis or protein mono(ADPribosyl)ation, respectively. At higher concentrations, PhAsO causes non-specific leakiness of mitochondria.
