Monitoring of Permeability Transition Pore Openings in Isolated Individual Brain Mitochondria

2017 ◽  
pp. 199-210 ◽  
Author(s):  
Nickolay Brustovetsky ◽  
Tatiana Brustovetsky
Keyword(s):  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Brain Mitochondria

scholarly journals Mild Hypoxemia during Initial Reperfusion Alleviates the Severity of Secondary Energy Failure and Protects Brain in Neonatal Mice with Hypoxic-Ischemic Injury

2011 ◽  
Vol 32 (2) ◽  
pp. 232-241 ◽  
Author(s):  
Zoya V Niatsetskaya ◽  
Pradeep Charlagorla ◽  
Dzmitry A Matsukevich ◽  
Sergey A Sosunov ◽  
Korapat Mayurasakorn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Oxygen Saturation ◽  
Infarct Volume ◽  
Birth Asphyxia ◽  
Permeability Transition Pore ◽  
Oxidative Injury ◽  
Permeability Transition ◽  
Brain Mitochondria ◽  
Mptp Opening

Reperfusion triggers an oxidative stress. We hypothesized that mild hypoxemia in reperfusion attenuates oxidative brain injury following hypoxia-ischemia (HI). In neonatal HI-mice, the reperfusion was initiated by reoxygenation with room air (RA) followed by the exposure to 100%, 21%, 18%, 15% oxygen for 60 minutes. Systemic oxygen saturation (SaO2), cerebral blood flow (CBF), brain mitochondrial respiration and permeability transition pore (mPTP) opening, markers of oxidative injury, and cerebral infarcts were assessed. Compared with RA-littermates, HI-mice exposed to 18% oxygen exhibited significantly decreased infarct volume, oxidative injury in the brain mitochondria and tissue. This was coupled with improved mitochondrial tolerance to mPTP opening. Oxygen saturation maintained during reperfusion at 85% to 95% was associated ( r=0.57) with the best neurologic outcome. Exposure to 100% or 15% oxygen significantly exacerbated brain injury and oxidative stress. Compared with RA-mice, hyperoxia dramatically increased reperfusion CBF, but exposure to 15% oxygen significantly reduced CBF to values observed during the HI-insult. Mild hypoxemia during initial reperfusion alleviates the severity of HI-brain injury by limiting the reperfusion-driven oxidative stress to the mitochondria and mPTP opening. This suggests that at the initial stage of reperfusion, a slightly decreased systemic oxygenation (SaO2 85% to 95%) may be beneficial for infants with birth asphyxia.

scholarly journals Amyloid β-Peptide Promotes Permeability Transition Pore in Brain Mitochondria

2001 ◽  
Vol 21 (6) ◽  
pp. 789-800 ◽  
Author(s):  
Paula I. Moreira ◽  
Maria S. Santos ◽  
António Moreno ◽  
Catarina Oliveira
Keyword(s):  
Transmembrane Potential ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Amyloid Β ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Brain Mitochondria ◽  
Amyloid Β Peptide ◽  
Mitochondrial Permeability ◽  
Pre Treatment

In this work the effect of the neurotoxic amino acid sequence, Aβ25–35, on brain mitochondrial permeability transition pore (PTP) was studied. For the purpose, the mitochondrial transmembrane potential (ΔΨm), mitochondrial respiration and the calcium fluxes were examined. It was observed that Aβ25–35, in the presence of Ca2+, decreased the ΔΨm, the capacity of brain mitochondria to accumulate calcium and led to a complete uncoupling of the respiration. However, the reverse sequence of the peptide Aβ25–35 (Aβ35–25) did not promote the PTP. The alterations promoted by Aβ35–25 and/or Ca2+ could be reversed when Ca2+ was removed by EGTA or when ADP plus oligomycin were present. The pre-treatment with CsA or ADP plus oligomycin prevented the ΔΨm drop and preserved the capacity of mitochondria to accumulate Ca2+. These results suggest that Aβ25–35 can promote the PTP induced by Ca2+.

scholarly journals NAD(H) Regulates the Permeability Transition Pore in Mitochondria through an External Site

2021 ◽  
Vol 22 (16) ◽  
pp. 8560
Author(s):  
Ekaterina Kharechkina ◽  
Anna Nikiforova ◽  
Alexey Kruglov
Keyword(s):  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Brain Mitochondria ◽  
Mitochondrial Swelling ◽  
Mitochondrial Depolarization ◽  
Retention Capacity ◽  
The Matrix ◽  
External Site ◽  
Dependent Site

The opening of the permeability transition pore (mPTP) in mitochondria initiates cell death in numerous diseases. The regulation of mPTP by NAD(H) in the mitochondrial matrix is well established; however, the role of extramitochondrial (cytosolic) NAD(H) is still unclear. We studied the effect of added NADH and NAD+ on: (1) the Ca2+-retention capacity (CRC) of isolated rat liver, heart, and brain mitochondria; (2) the Ca2+-dependent mitochondrial swelling in media whose particles can (KCl) or cannot (sucrose) be extruded from the matrix by mitochondrial carriers; (3) the Ca2+-dependent mitochondrial depolarization and the release of entrapped calcein from mitochondria of permeabilized hepatocytes; and (4) the Ca2+-dependent mitochondrial depolarization and subsequent repolarization. NADH and NAD+ increased the CRC of liver, heart, and brain mitochondria 1.5–2.5 times, insignificantly affecting the rate of Ca2+-uptake and the free Ca2+ concentration in the medium. NAD(H) suppressed the Ca2+-dependent mitochondrial swelling both in KCl- and sucrose-based media but did not induce the contraction and repolarization of swollen mitochondria. By contrast, EGTA caused mitochondrial repolarization in both media and the contraction in KCl-based medium only. NAD(H) delayed the Ca2+-dependent depolarization and the release of calcein from individual mitochondria in hepatocytes. These data unambiguously demonstrate the existence of an external NAD(H)-dependent site of mPTP regulation.

scholarly journals Possible Involvement of 2′,3′-Cyclic Nucleotide-3′-Phosphodiesterase in the Protein Phosphorylation-Mediated Regulation of the Permeability Transition Pore

2018 ◽  
Vol 19 (11) ◽  
pp. 3499 ◽  
Author(s):  
Yulia Baburina ◽  
Irina Odinokova ◽  
Tamara Azarashvili ◽  
Vladimir Akatov ◽  
Linda Sotnikova ◽  
...  
Keyword(s):  
Protein Phosphorylation ◽  
Rat Brain ◽  
Protein Kinases ◽  
Cyclic Nucleotide ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Brain Mitochondria ◽  
Calmodulin Antagonist ◽  
Rat Brain Mitochondria ◽  
Mptp Opening

Calcium as a secondary messenger regulates the phosphorylation of several membrane-bound proteins in brain and liver mitochondria. Regulation of the activity of different protein kinases and phosphatases by Ca2+ occurs through its binding with calmodulin. The protein phosphorylation is strongly dependent on the Ca2+-induced mitochondrial permeability transition pore (mPTP) opening. 2′,3′-Cyclic nucleotide-3′-phosphodiesterase (CNPase) was phosphorylated by protein kinases A and C. CNPase and melatonin (MEL) might interact with calmodulin. The effects of the calmodulin antagonist calmidazolium and the inhibitor of protein kinase A H89 on mPTP opening in rat brain mitochondria of male Wistar rats were investigated. In addition, the role of CNPase, serine/threonine kinases, and MEL in the mPTP opening was examined. The anti-CNPase antibody added to rat brain mitochondria (RBM) reduced the content of CNPase in mitochondria. The threshold [Ca2+] decreased, and mitochondrial swelling was accelerated in the presence of the anti-CNPase antibody. H89 enhanced the effect of anti-CNPase antibody and accelerated the swelling of mitochondria, while CmZ abolished the effect of anti-CNPase antibody under mPTP opening. The levels of phospho-Akt and phospho-GSK3β increased, while the MEL content did not change. It can be assumed that CNPase may be involved in the regulation of these kinases, which in turn plays an important role in mPTP functioning.

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