scholarly journals Cyclosporine A attenuates mitochondrial permeability transition and improves mitochondrial respiratory function in cardiomyocytes isolated from dogs with heart failure

2007 ◽  
Vol 42 (1) ◽  
pp. 150-158 ◽  
Author(s):  
Victor G. Sharov ◽  
Anastassia Todor ◽  
Sanjaya Khanal ◽  
Makoto Imai ◽  
Hani N. Sabbah
Keyword(s):  
Heart Failure ◽  
Cyclosporine A ◽  
Respiratory Function ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
Mitochondrial Respiratory

scholarly journals On the Mechanism(s) of Membrane Permeability Transition in Liver Mitochondria of Lamprey,Lampetra fluviatilis L.: Insights from Cadmium

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Elena A. Belyaeva ◽  
Larisa V. Emelyanova ◽  
Sergey M. Korotkov ◽  
Irina V. Brailovskaya ◽  
Margarita V. Savina
Keyword(s):  
Membrane Permeability ◽  
Cyclosporine A ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Nitrate Medium ◽  
Lampetra Fluviatilis ◽  
Mitochondrial Permeability

Previously we have shown that opening of the mitochondrial permeability transition pore in its low conductance state is the case in hepatocytes of the Baltic lamprey (Lampetra fluviatilis L.) during reversible metabolic depression taking place in the period of its prespawning migration when the exogenous feeding is switched off. The depression is observed in the last year of the lamprey life cycle and is conditioned by reversible mitochondrial dysfunction (mitochondrial uncoupling in winter and coupling in spring). To further elucidate the mechanism(s) of induction of the mitochondrial permeability transition pore in the lamprey liver, we used Cd2+and Ca2+plus Pias the pore inducers. We found that Ca2+plus Piinduced the high-amplitude swelling of the isolated “winter” mitochondria both in isotonic sucrose and ammonium nitrate medium while both low and high Cd2+did not produce the mitochondrial swelling in these media. Low Cd2+enhanced the inhibition of basal respiration rate of the “winter” mitochondria energized by NAD-dependent substrates whereas the same concentrations of the heavy metal evoked its partial stimulation on FAD-dependent substrates. The above changes produced by Cd2+or Ca2+plus Piin the “winter” mitochondria were only weakly (if so) sensitive to cyclosporine A (a potent pharmacological desensitizer of the nonselective pore) added alone and they were not sensitive to dithiothreitol (a dithiol reducing agent). Under monitoring of the transmembrane potential of the “spring” lamprey liver mitochondria, we revealed that Cd2+produced its decrease on both types of the respiratory substrates used that was strongly hampered by cyclosporine A, and the membrane potential was partially restored by dithiothreitol. The effects of different membrane permeability modulators on the lamprey liver mitochondria function and the seasonal changes in their action are discussed.

Postconditioning With Cyclosporine A Reduces Early Renal Dysfunction by Inhibiting Mitochondrial Permeability Transition

2015 ◽  
Vol 99 (4) ◽  
pp. 717-723 ◽  
Author(s):  
Sandrine Lemoine ◽  
Bruno Pillot ◽  
Nicolas Rognant ◽  
Lionel Augeul ◽  
Maud Rayberin ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Cyclosporine A ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitochondrial Permeability

scholarly journals Tissue Specific Sensitivity of Mitochondrial Permeability Transition Pore to Ca2+ Ions

2009 ◽  
Vol 52 (2) ◽  
pp. 69-72 ◽  
Author(s):  
René Endlicher ◽  
Pavla Křiváková ◽  
Halka Lotková ◽  
Marie Milerová ◽  
Zdeněk Drahota ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Swelling ◽  
Heart Mitochondria ◽  
Cell Protection ◽  
Tissue Specific ◽  
Mitochondrial Permeability

Ca2+-induced opening of the mitochondrial permeability transition pore (MPTP) is involved in induction of apoptotic and necrotic processes. We studied sensitivity of MPTP to calcium using the model of Ca2+-induced, cyclosporine A-sensitive mitochondrial swelling. Presented data indicate that the extent of mitochondrial swelling (dA520/4 min) induced by addition of 25 μM Ca2+ is seven-fold higher in liver than in heart mitochondria (0.564 ± 0.08/0.077± 0.01). The extent of swelling induced by 100 μM Ca2+ was in liver tree times higher than in heart mitochondria (0.508±0.05/ 0.173±0.02). Cyclosporine A sensitivity showed that opening of the MPTP is involved. We may thus conclude that especially at low Ca2+ concentration heart mitochondria are more resistant to damaging effect of Ca2+ than liver mitochondria. These finding thus support hypothesis that there exist tissue specific strategies of cell protection against induction of the apoptotic and necrotic processes.

Abstract 16743: A Kinase Interacting Protein 1 Does Not Protect From Adverse Cardiac Remodelling but Attenuates Myocardial Ischemia - Reperfusion Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Harmen G Booij ◽  
Hongjuan Yu ◽  
Rudolf A de Boer ◽  
Wiek H van Gilst ◽  
Herman H Silljé ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Wild Type ◽  
Interacting Protein ◽  
Mitochondrial Permeability ◽  
Myocardial Ischemia Reperfusion

Introduction: A kinase interacting protein 1 (AKIP1) attenuates myocardial ischemia / reperfusion (I/R) injury and stimulates beneficial cardiac remodeling in cultured cardiomyocytes. Whether these findings translate into functional benefits in vivo remains to be established. Hypothesis: We assessed the hypothesis that cardiac overexpression of AKIP1 attenuates myocardial heart failure development or I/R-injury in mice. Methods: We created transgenic mice with cardiac-specific overexpression of AKIP1 (AKIP1-TG). First, AKIP1-TG mice or their wild type littermates were subjected to transverse aortic constriction (TAC) and myocardial infarction (MI) with permanent ligation of the left coronary artery. Second, infarct size after 45 minutes ischemia followed by 24h reperfusion was assessed with Evans Bleu and triphenyltetrazolium chloride staining. Results: AKIP1-TG mice and wild type littermates displayed similar left ventricular remodeling and function after TAC or MI as measured with magnetic resonance imaging. Histological indices of heart failure severity, including cardiomyocyte cross-sectional area, capillary density and fibrosis were also similar. However, infarct size relative to the area at risk was reduced 2-fold in AKIP1-TG mice after I/R (15% ± 3 vs. 29± 4 %, p<0,05) and accompanied with a marked reduction in apoptosis (5,4 ± 0,5% vs. 8,1 ± 1,1%, p<0,05). AKIP1 overexpression did not influence cardiac transcription or signaling. Subcellular fraction studies showed enrichment of AKIP1 in mitochondria. In addition, AKIP1 attenuated calcium induced swelling of mitochondria (0.77 ± 0.01 vs. 0.71 ± 0.01, p<0.05), suggesting a direct role for AKIP1 in the mitochondrial permeability transition pore. Conclusions: In conclusion, AKIP1 does not influence cardiac remodeling in models of chronic heart failure. However, AKIP1 does attenuate myocardial I/R injury through stabilization of the mitochondrial permeability transition pore.

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