Open Access

Global brain ischemia in rats is associated with mitochondrial release and downregulation of Mfn2 in the cerebral cortex, but not the hippocampus

  • Authors:
    • Katarina Klacanova
    • Maria Kovalska
    • Maria Chomova
    • Ivana Pilchova
    • Zuzana Tatarkova
    • Peter Kaplan
    • Peter Racay
  • View Affiliations

  • Published online on: April 16, 2019     https://doi.org/10.3892/ijmm.2019.4168
  • Pages: 2420-2428
  • Copyright: © Klacanova et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitochondria are crucial for neuronal cell survival and death through their functions in ATP production and the intrinsic pathway of apoptosis. Mitochondrial dysfunction is considered to play a central role in several serious human diseases, including neurodegenerative diseases, such as Parkinson's and Alzheimer's disease and ischemic neurodegeneration. The aim of the present study was to investigate the impact of transient global brain ischemia on the expression of selected proteins involved in mitochondrial dynamics and mitochondria‑associated membranes. The main foci of interest were the proteins mitofusin 2 (Mfn2), dynamin‑related protein 1 (DRP1), voltage‑dependent anion‑selective channel 1 (VDAC1) and glucose‑regulated protein 75 (GRP75). Western blot analysis of total cell extracts and mitochondria isolated from either the cerebral cortex or hippocampus of experimental animals was performed. In addition, Mfn2 was localized intracellularly by laser scanning confocal microscopy. It was demonstrated that 15‑min ischemia, or 15‑min ischemia followed by 1, 3, 24 or 72 h of reperfusion, was associated with a marked decrease of the Mfn2 protein in mitochondria isolated from the cerebral cortex, but not in hippocampal mitochondria. Moreover, a translocation of the Mfn2 protein to the cytoplasm was documented immediately after global brain ischemia in the neurons of the cerebral cortex by laser scanning confocal microscopy. Mfn2 translocation was followed by decreased expression of Mfn2 during reperfusion. Markedly elevated levels of the VDAC1 protein were also documented in total cell extracts isolated from the hippocampus of rats after 15 min of global brain ischemia followed by 3 h of reperfusion, and from the cerebral cortex of rats after 15 min of global brain ischemia followed by 72 h of reperfusion. The mitochondrial Mfn2 release observed during the early stages of reperfusion may thus represent an important mechanism of mitochondrial dysfunction associated with neuronal dysfunction or death induced by global brain ischemia.

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June 2019
Volume 43 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
APA
Klacanova, K., Kovalska, M., Chomova, M., Pilchova, I., Tatarkova, Z., Kaplan, P., & Racay, P. (2019). Global brain ischemia in rats is associated with mitochondrial release and downregulation of Mfn2 in the cerebral cortex, but not the hippocampus. International Journal of Molecular Medicine, 43, 2420-2428. https://doi.org/10.3892/ijmm.2019.4168
MLA
Klacanova, K., Kovalska, M., Chomova, M., Pilchova, I., Tatarkova, Z., Kaplan, P., Racay, P."Global brain ischemia in rats is associated with mitochondrial release and downregulation of Mfn2 in the cerebral cortex, but not the hippocampus". International Journal of Molecular Medicine 43.6 (2019): 2420-2428.
Chicago
Klacanova, K., Kovalska, M., Chomova, M., Pilchova, I., Tatarkova, Z., Kaplan, P., Racay, P."Global brain ischemia in rats is associated with mitochondrial release and downregulation of Mfn2 in the cerebral cortex, but not the hippocampus". International Journal of Molecular Medicine 43, no. 6 (2019): 2420-2428. https://doi.org/10.3892/ijmm.2019.4168