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

Baburina, Yulia; Odinokova, Irina; Azarashvili, Tamara; Akatov, Vladimir; Sotnikova, Linda; Krestinina, Olga

doi:10.3390/ijms19113499

Open AccessArticle

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

by

Yulia Baburina

,

Irina Odinokova

,

Tamara Azarashvili

,

Vladimir Akatov

,

Linda Sotnikova

and

Olga Krestinina

^*

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino 142290, Russia

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2018, 19(11), 3499; https://doi.org/10.3390/ijms19113499

Submission received: 16 October 2018 / Revised: 4 November 2018 / Accepted: 5 November 2018 / Published: 7 November 2018

(This article belongs to the Special Issue Protein Phosphorylation in Health and Disease)

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Abstract

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.

Keywords: permeability transition pore; protein phosphorylation; serine/threonine kinases; calmodulin; 2′,3′-cyclic nucleotide 3′-phosphodiesterase; melatonin

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Baburina, Y.; Odinokova, I.; Azarashvili, T.; Akatov, V.; Sotnikova, L.; Krestinina, O. Possible Involvement of 2′,3′-Cyclic Nucleotide-3′-Phosphodiesterase in the Protein Phosphorylation-Mediated Regulation of the Permeability Transition Pore. Int. J. Mol. Sci. 2018, 19, 3499. https://doi.org/10.3390/ijms19113499

AMA Style

Baburina Y, Odinokova I, Azarashvili T, Akatov V, Sotnikova L, Krestinina O. Possible Involvement of 2′,3′-Cyclic Nucleotide-3′-Phosphodiesterase in the Protein Phosphorylation-Mediated Regulation of the Permeability Transition Pore. International Journal of Molecular Sciences. 2018; 19(11):3499. https://doi.org/10.3390/ijms19113499

Chicago/Turabian Style

Baburina, Yulia, Irina Odinokova, Tamara Azarashvili, Vladimir Akatov, Linda Sotnikova, and Olga Krestinina. 2018. "Possible Involvement of 2′,3′-Cyclic Nucleotide-3′-Phosphodiesterase in the Protein Phosphorylation-Mediated Regulation of the Permeability Transition Pore" International Journal of Molecular Sciences 19, no. 11: 3499. https://doi.org/10.3390/ijms19113499

APA Style

Baburina, Y., Odinokova, I., Azarashvili, T., Akatov, V., Sotnikova, L., & Krestinina, O. (2018). Possible Involvement of 2′,3′-Cyclic Nucleotide-3′-Phosphodiesterase in the Protein Phosphorylation-Mediated Regulation of the Permeability Transition Pore. International Journal of Molecular Sciences, 19(11), 3499. https://doi.org/10.3390/ijms19113499

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

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