The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria

Cell Calcium ◽  
2007 ◽  
Vol 42 (1) ◽  
pp. 27-39 ◽  
Author(s):  
Tamara Azarashvili ◽  
Dmitry Grachev ◽  
Olga Krestinina ◽  
Youri Evtodienko ◽  
Igor Yurkov ◽  
...  
Keyword(s):  
Rat Brain ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Benzodiazepine Receptor ◽  
Brain Mitochondria ◽  
Rat Brain Mitochondria ◽  
Permeability Transition Pore Opening ◽  
Pore Opening ◽  
Peripheral Type

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.

Calcium-induced permeability transition in rat brain mitochondria is promoted by carbenoxolone through targeting connexin43

2011 ◽  
Vol 300 (3) ◽  
pp. C707-C720 ◽  
Author(s):  
Tamara Azarashvili ◽  
Yulia Baburina ◽  
Dmitry Grachev ◽  
Olga Krestinina ◽  
Yuri Evtodienko ◽  
...  
Keyword(s):  
Rat Brain ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Brain Mitochondria ◽  
Molecular Target ◽  
Threshold Concentration ◽  
Rat Liver Mitochondria ◽  
Rat Brain Mitochondria ◽  
Synaptic Mitochondria ◽  
Ptp Opening

Carbenoxolone (Cbx), a substance from medicinal licorice, is used for antiinflammatory treatments. We investigated the mechanism of action of Cbx on Ca2+-induced permeability transition pore (PTP) opening in synaptic and nonsynaptic rat brain mitochondria (RBM), as well as in rat liver mitochondria (RLM), in an attempt to identify the molecular target of Cbx in mitochondria. Exposure to threshold Ca2+ load induced PTP opening, as seen by sudden Ca2+ efflux from the mitochondrial matrix and membrane potential collapse. In synaptic RBM, Cbx (1 μM) facilitated the Ca2+-induced, cyclosporine A-sensitive PTP opening, while in nonsynaptic mitochondria the Cbx threshold concentration was higher. A well-known molecular target of Cbx is the connexin (Cx) family, gap junction proteins. Moreover, Cx43 was previously found in heart mitochondria and attributed to the preconditioning mechanism of protection. Thus, we hypothesized that Cx43 might be a target for Cbx in brain mitochondria. For the first time, we detected Cx43 by Western blot in RBM, but Cx43 was absent in RLM. Interestingly, two anti-Cx43 antibodies, directed against amino acids 252 to 270 of rat Cx43, abolished the Cbx-induced enhancement of PTP opening in total RBM and in synaptic mitochondria, but not in RLM. In total RBM and in synaptic mitochondria, PTP caused dephosphorylation of Cx43 at serine 368. The phosphorylation level of serine 368 was decreased at threshold calcium concentration and additionally in the combined presence of Cbx in synaptic mitochondria. In conclusion, active mitochondrial Cx43 appears to counteract the Ca2+-induced PTP opening and thus might inhibit the PTP-ensuing mitochondrial demise and cell death. Consequently, we suggest that activity of Cx43 in brain mitochondria represents a novel molecular target for protection.

Sign in / Sign up

Export Citation Format

Share Document