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Difference between revisions of "Tretter 2012 Free Radic Biol Med"

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{{Publication
{{Publication
|title=Tretter L, Adam-Vizi V (2012) High Ca<sup>2+</sup> load promotes hydrogen peroxide generation via activation of α-glycerophosphate dehydrogenase in brain mitochondria. Free Radic Biol Med 53: 2119-21130
|title=Tretter Laszlo, Adam-Vizi Vera (2012) High Ca<sup>2+</sup> load promotes hydrogen peroxide generation via activation of α-glycerophosphate dehydrogenase in brain mitochondria. Free Radic Biol Med 53:2119-30.
|info=[http://www.ncbi.nlm.nih.gov/pubmed/23022874 PMID: 23022874]
|info=[http://www.ncbi.nlm.nih.gov/pubmed/23022874 PMID: 23022874]
|authors=Tretter L, Adam-Vizi V
|authors=Tretter Laszlo, Adam-Vizi Vera
|year=2012
|year=2012
|journal=Free Radic Biol Med
|journal=Free Radic Biol Med
|abstract=H<sub>2</sub>O<sub>2</sub> generation associated with α-glycerophosphate (α-GP) oxidation was addressed in guinea pig brain mitochondria challenged with high Ca<sup>2+</sup> load (10 μM). Exposure to 10 μM Ca<sup>2+</sup> induced an abrupt 2.5-fold increase in H<sub>2</sub>O<sub>2</sub> release compared to that measured in the presence of a physiological cytosolic Ca<sup>2+</sup> concentration (100 nM) from mitochondria respiring on 5 mM α-GP in the presence of ADP (2 mM). The Ca<sup>2+</sup>-induced stimulation of H<sub>2</sub>O<sub>2</sub> generation was reversible and unaltered by the uniporter blocker Ru 360, indicating that it did not require Ca<sup>2+</sup> uptake into mitochondria. Enhanced H<sub>2</sub>O<sub>2</sub> generation by Ca<sup>2+</sup> was also observed in the absence of ADP when mitochondria exhibited permeability transition pore opening with a decrease in the NAD(P)H level, dissipation of membrane potential, and mitochondrial swelling. Furthermore, mitochondria treated with the pore-forming peptide alamethicin also responded with an elevated H<sub>2</sub>O<sub>2</sub> generation to a challenge with 10 μM Ca<sup>2+</sup>. Ca<sup>2+</sup>-induced promotion of H<sub>2</sub>O<sub>2</sub> formation was further enhanced by the complex III inhibitor myxothiazol. With 20 mM α-GP concentration, stimulation of H<sub>2</sub>O<sub>2</sub> formation by Ca<sup>2+</sup> was detected only in the presence, not in the absence, of ADP. It is concluded that α-glycerophosphate dehydrogenase, which is accessible to and could be activated by a rise in the level of cytosolic Ca<sup>2+</sup>, makes a major contribution to Ca<sup>2+</sup>-stimulated H<sub>2</sub>O<sub>2</sub> generation. This work highlights a unique high-Ca<sup>2+</sup>-stimulated reactive oxygen species-forming mechanism in association with oxidation of α-GP, which is largely independent of the bioenergetic state and can proceed even in damaged, functionally incompetent mitochondria.
|abstract=H<sub>2</sub>O<sub>2</sub> generation associated with α-glycerophosphate (α-GP) oxidation was addressed in guinea pig brain mitochondria challenged with high Ca<sup>2+</sup> load (10 μM). Exposure to 10 μM Ca<sup>2+</sup> induced an abrupt 2.5-fold increase in H<sub>2</sub>O<sub>2</sub> release compared to that measured in the presence of a physiological cytosolic Ca<sup>2+</sup> concentration (100 nM) from mitochondria respiring on 5 mM α-GP in the presence of ADP (2 mM). The Ca<sup>2+</sup>-induced stimulation of H<sub>2</sub>O<sub>2</sub> generation was reversible and unaltered by the uniporter blocker Ru 360, indicating that it did not require Ca<sup>2+</sup> uptake into mitochondria. Enhanced H<sub>2</sub>O<sub>2</sub> generation by Ca<sup>2+</sup> was also observed in the absence of ADP when mitochondria exhibited permeability transition pore opening with a decrease in the NAD(P)H level, dissipation of membrane potential, and mitochondrial swelling. Furthermore, mitochondria treated with the pore-forming peptide alamethicin also responded with an elevated H<sub>2</sub>O<sub>2</sub> generation to a challenge with 10 μM Ca<sup>2+</sup>. Ca<sup>2+</sup>-induced promotion of H<sub>2</sub>O<sub>2</sub> formation was further enhanced by the Complex III inhibitor myxothiazol. With 20 mM α-GP concentration, stimulation of H<sub>2</sub>O<sub>2</sub> formation by Ca<sup>2+</sup> was detected only in the presence, not in the absence, of ADP. It is concluded that [[Glycerophosphate dehydrogenase complex |α-glycerophosphate dehydrogenase]], which is accessible to and could be activated by a rise in the level of cytosolic Ca<sup>2+</sup>, makes a major contribution to Ca<sup>2+</sup>-stimulated H<sub>2</sub>O<sub>2</sub> generation. This work highlights a unique high-Ca<sup>2+</sup>-stimulated reactive oxygen species-forming mechanism in association with oxidation of α-GP, which is largely independent of the bioenergetic state and can proceed even in damaged, functionally incompetent mitochondria.
|keywords=Mitochondria; Reactive oxygen species; Calcium; Hydrogen peroxide; α-Glycerophosphate dehydrogenase; Reverse electron transport; Permeability transition pore; Myxothiazol; α-Glycerophosphate shuttle; Free radicals
|keywords=Mitochondria; Reactive oxygen species; Calcium; Hydrogen peroxide; α-Glycerophosphate dehydrogenase; Reverse electron transport; Permeability transition pore; Myxothiazol; α-Glycerophosphate shuttle; Free radicals
|mipnetlab=HU_Budapest_Tretter L, HU Budapest Semmelweis Univ
|mipnetlab=HU_Budapest_Tretter L
}}
}}
{{Labeling
{{Labeling
|instruments=Oxygraph-2k, Spectrofluorometry
|area=Respiration
|injuries=RONS; Oxidative Stress
|organism=Guinea pig
|organism=Guinea pig
|tissues=Neurons; Brain
|tissues=Nervous system
|preparations=Isolated Mitochondria
|preparations=Isolated mitochondria
|substratestates=GpDH
|injuries=Oxidative stress;RONS
|enzymes=Complex III
|pathways=Gp
|instruments=Oxygraph-2k
|additional=Fura-6F; Amplex Red; Safranin
|additional=Fura-6F; Amplex Red; Safranin
}}
}}

Revision as of 09:34, 27 July 2020

Publications in the MiPMap
Tretter Laszlo, Adam-Vizi Vera (2012) High Ca2+ load promotes hydrogen peroxide generation via activation of α-glycerophosphate dehydrogenase in brain mitochondria. Free Radic Biol Med 53:2119-30.

» PMID: 23022874

Tretter Laszlo, Adam-Vizi Vera (2012) Free Radic Biol Med

Abstract: H2O2 generation associated with α-glycerophosphate (α-GP) oxidation was addressed in guinea pig brain mitochondria challenged with high Ca2+ load (10 μM). Exposure to 10 μM Ca2+ induced an abrupt 2.5-fold increase in H2O2 release compared to that measured in the presence of a physiological cytosolic Ca2+ concentration (100 nM) from mitochondria respiring on 5 mM α-GP in the presence of ADP (2 mM). The Ca2+-induced stimulation of H2O2 generation was reversible and unaltered by the uniporter blocker Ru 360, indicating that it did not require Ca2+ uptake into mitochondria. Enhanced H2O2 generation by Ca2+ was also observed in the absence of ADP when mitochondria exhibited permeability transition pore opening with a decrease in the NAD(P)H level, dissipation of membrane potential, and mitochondrial swelling. Furthermore, mitochondria treated with the pore-forming peptide alamethicin also responded with an elevated H2O2 generation to a challenge with 10 μM Ca2+. Ca2+-induced promotion of H2O2 formation was further enhanced by the Complex III inhibitor myxothiazol. With 20 mM α-GP concentration, stimulation of H2O2 formation by Ca2+ was detected only in the presence, not in the absence, of ADP. It is concluded that α-glycerophosphate dehydrogenase, which is accessible to and could be activated by a rise in the level of cytosolic Ca2+, makes a major contribution to Ca2+-stimulated H2O2 generation. This work highlights a unique high-Ca2+-stimulated reactive oxygen species-forming mechanism in association with oxidation of α-GP, which is largely independent of the bioenergetic state and can proceed even in damaged, functionally incompetent mitochondria. Keywords: Mitochondria; Reactive oxygen species; Calcium; Hydrogen peroxide; α-Glycerophosphate dehydrogenase; Reverse electron transport; Permeability transition pore; Myxothiazol; α-Glycerophosphate shuttle; Free radicals

O2k-Network Lab: HU_Budapest_Tretter L


Labels: MiParea: Respiration 

Stress:Oxidative stress;RONS  Organism: Guinea pig  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 


Pathway: Gp  HRR: Oxygraph-2k 

Fura-6F; Amplex Red; Safranin