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Activation of GPR81 lactate receptors stimulates mitochondrial biogenesis in cerebral microvessel endothelial cells
- Authors: Khilazheva E.D.1, Pisareva N.V.1, Morgun A.V.1, Boitsova E.B.1, Taranushenko T.E.1, Frolova O.V.1, Salmina A.B.1
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Affiliations:
- Research Institute of Molecular Medicine and Pathobiochemistry, V.F. Voino-Yasenetskii Krasnoyarsk State Medical University
- Issue: Vol 11, No 1 (2017)
- Pages: 34-39
- Section: Original articles
- URL: https://annaly-nevrologii.com/journal/pathID/article/view/457
- DOI: https://doi.org/10.18454/ACEN.2017.1.6155
- ID: 457
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Abstract
Introduction. Cerebral endothelial cells express monocarboxylate transporters MCT1 for blood–brain barrier (BBB) transfer of lactate, which are regulated by CD147 activity, as well as lactate receptors GPR81 (HCAR1). Metabolism and intercellular transport of lactate is the crucial mechanism for regulating the function of BBB cells.
Objective. To study the effect of activity of GPR81 receptors in cerebral endothelial cells on expression of MCT1, CD147 and the mitochondrial dynamics, which will make it possible to explain the effect of local production of lactate by perivascular astrocytes on angiogenesis in the cerebral tissue.
Materials and methods. The culture of cerebral endothelial cells isolated from the brain of 15–17-day-old Wistar rat embryos was used in this study. Mitochondrial biogenesis of cerebral endothelial cells was studied using the standard MitoBiogenesis In-Cell ELISA Kit protocol (Abcam). Chemical hypoxia was induced by incubation in the presence of 50 μM iodoacetate for 30 min. 3Cl-5OH-BA (Calbiochem) at concentrations of 5, 50, and 500 μM was used as an agonist of GPR81 lactate receptors during 24 h. The number of cells expressing GPR81, CD147, and MCT1 molecules was evaluated using indirect double-antibody ELISA.
Results. It was found for the first time that prolonged dose-dependent stimulation of GPR81 receptors with 3Cl-5OH-BA intensifies mitochondrial biogenesis (up to 1.5-fold, р<0.05). Meanwhile, a statistically significant (p<0.05) inhibition of expression of monocarboxylate transporters MCT1 (from 81±1.6% to 40.7±4.4%) and the conjugated CD147 protein (from 57.4±3.3% to 48.3±2.9%) in cerebral endothelial cells in the study group compared to the control group.
Conclusions. The findings broaden the range of potential applications of GPR81 agonists for modulating intercellular interactions in a neurovascular unit and controlling the functional activity of cerebral microvessel endothelial cells.
About the authors
E. D. Khilazheva
Research Institute of Molecular Medicine and Pathobiochemistry, V.F. Voino-Yasenetskii Krasnoyarsk State Medical University
Email: allasalmina@mail.ru
Russian Federation, Krasnoyarsk
N. V. Pisareva
Research Institute of Molecular Medicine and Pathobiochemistry, V.F. Voino-Yasenetskii Krasnoyarsk State Medical University
Email: allasalmina@mail.ru
Russian Federation, Krasnoyarsk
A. V. Morgun
Research Institute of Molecular Medicine and Pathobiochemistry, V.F. Voino-Yasenetskii Krasnoyarsk State Medical University
Email: allasalmina@mail.ru
Russian Federation, Krasnoyarsk
E. B. Boitsova
Research Institute of Molecular Medicine and Pathobiochemistry, V.F. Voino-Yasenetskii Krasnoyarsk State Medical University
Email: allasalmina@mail.ru
Russian Federation, Krasnoyarsk
T. E. Taranushenko
Research Institute of Molecular Medicine and Pathobiochemistry, V.F. Voino-Yasenetskii Krasnoyarsk State Medical University
Email: allasalmina@mail.ru
Russian Federation, Krasnoyarsk
O. V. Frolova
Research Institute of Molecular Medicine and Pathobiochemistry, V.F. Voino-Yasenetskii Krasnoyarsk State Medical University
Email: allasalmina@mail.ru
Russian Federation, Krasnoyarsk
Alla B. Salmina
Research Institute of Molecular Medicine and Pathobiochemistry, V.F. Voino-Yasenetskii Krasnoyarsk State Medical University
Author for correspondence.
Email: allasalmina@mail.ru
Russian Federation, Krasnoyarsk
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Supplementary files
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).