Inhibition of Mitochondrial Na+-Dependent Ca2+ Efflux By 17 Beta-Estradiol in the Rat Hippocampus
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Аутори
Petrović, S.Velickovic, N.
Stanojević, Ivana
Milošević, Maja
Drakulić, Dunja R.
Stanojlović, Miloš R.
Horvat, Anica
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Метаподаци
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Our results, as well as those of others, have indicated that 17 beta-estradiol (E2) exerts its nongenomic effects in neuronal cells by affecting plasma membrane Ca2+ flux. In neuronal cells mitochondria possess Ca2+ buffering properties as they both sequester and release Ca2+. The goal of this study was to examine the rapid non-genomic effect of E2 on mitochondria! Ca2+ transport in hippocampal synaptosomes from ovariectomised rats. In addition, we aimed to determine if, and to what extent, E2 receptors participated in mitochondria! Ca2+ transport modulation by E2 in vitro. E2-specific binding and Ca2+ transport was monitored. At physiological E2 concentrations (0.1-1.5 nmol/L), specific E2 binding to mitochondria isolated from hippocampal synaptosomes was detected with a B-max and K-m of 37.6 +/- 2.6 fmol/mg protein and 0.69 +/- 0.14 nmol/L of free E2, respectively. The main mitochondrial Ca2+ influx mechanism is the Ruthenium Red-sensitive uniporter driven by mitochondrial membrane p...otential. Despite no effect of E2 on Ca2+ influx, a physiological E2 concentration (0.5 nmol/L) protected mitochondrial membrane potential and consequently Ca2+ influx from the uncoupling agent carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (1 mu mol/L). In neuronal cells the predominant mitochondria! Ca2+ efflux mechanism is the Na+/Ca2+ exchanger. E2 caused Ca2+ efflux inhibition (by 46%) coupled with increased affinity of the Na+/Ca2+ exchanger for Na+. Using E2 receptor (ER alpha and ER beta) antagonists and agonists, we confirmed ER betas involvement in E2-induced mitochondrial membrane potential protection as well as Ca2+ efflux inhibition. In summary, our results indicate that the nongenomic neuromodulatory role of E2 in rat hippocampus is achieved by affecting mitochondria! Ca2+ transport via, in part, mitochondrial ER beta. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
Кључне речи:
mitochondria / Ca2+ transport / estradiol / estradiol receptors / rat hippocampusИзвор:
Neuroscience, 2011, 192, 195-204Финансирање / пројекти:
- Молекуларни механизми патофизиолошких промена у ћелијама централног нервног система и периферног ткива код сисара (RS-MESTD-Basic Research (BR or ON)-173044)
DOI: 10.1016/j.neuroscience.2011.06.030
ISSN: 0306-4522
PubMed: 21726603
WoS: 000295555100019
Scopus: 2-s2.0-80052261110
Колекције
Институција/група
VinčaTY - JOUR AU - Petrović, S. AU - Velickovic, N. AU - Stanojević, Ivana AU - Milošević, Maja AU - Drakulić, Dunja R. AU - Stanojlović, Miloš R. AU - Horvat, Anica PY - 2011 UR - https://vinar.vin.bg.ac.rs/handle/123456789/4512 AB - Our results, as well as those of others, have indicated that 17 beta-estradiol (E2) exerts its nongenomic effects in neuronal cells by affecting plasma membrane Ca2+ flux. In neuronal cells mitochondria possess Ca2+ buffering properties as they both sequester and release Ca2+. The goal of this study was to examine the rapid non-genomic effect of E2 on mitochondria! Ca2+ transport in hippocampal synaptosomes from ovariectomised rats. In addition, we aimed to determine if, and to what extent, E2 receptors participated in mitochondria! Ca2+ transport modulation by E2 in vitro. E2-specific binding and Ca2+ transport was monitored. At physiological E2 concentrations (0.1-1.5 nmol/L), specific E2 binding to mitochondria isolated from hippocampal synaptosomes was detected with a B-max and K-m of 37.6 +/- 2.6 fmol/mg protein and 0.69 +/- 0.14 nmol/L of free E2, respectively. The main mitochondrial Ca2+ influx mechanism is the Ruthenium Red-sensitive uniporter driven by mitochondrial membrane potential. Despite no effect of E2 on Ca2+ influx, a physiological E2 concentration (0.5 nmol/L) protected mitochondrial membrane potential and consequently Ca2+ influx from the uncoupling agent carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (1 mu mol/L). In neuronal cells the predominant mitochondria! Ca2+ efflux mechanism is the Na+/Ca2+ exchanger. E2 caused Ca2+ efflux inhibition (by 46%) coupled with increased affinity of the Na+/Ca2+ exchanger for Na+. Using E2 receptor (ER alpha and ER beta) antagonists and agonists, we confirmed ER betas involvement in E2-induced mitochondrial membrane potential protection as well as Ca2+ efflux inhibition. In summary, our results indicate that the nongenomic neuromodulatory role of E2 in rat hippocampus is achieved by affecting mitochondria! Ca2+ transport via, in part, mitochondrial ER beta. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved. T2 - Neuroscience T1 - Inhibition of Mitochondrial Na+-Dependent Ca2+ Efflux By 17 Beta-Estradiol in the Rat Hippocampus VL - 192 SP - 195 EP - 204 DO - 10.1016/j.neuroscience.2011.06.030 ER -
@article{ author = "Petrović, S. and Velickovic, N. and Stanojević, Ivana and Milošević, Maja and Drakulić, Dunja R. and Stanojlović, Miloš R. and Horvat, Anica", year = "2011", abstract = "Our results, as well as those of others, have indicated that 17 beta-estradiol (E2) exerts its nongenomic effects in neuronal cells by affecting plasma membrane Ca2+ flux. In neuronal cells mitochondria possess Ca2+ buffering properties as they both sequester and release Ca2+. The goal of this study was to examine the rapid non-genomic effect of E2 on mitochondria! Ca2+ transport in hippocampal synaptosomes from ovariectomised rats. In addition, we aimed to determine if, and to what extent, E2 receptors participated in mitochondria! Ca2+ transport modulation by E2 in vitro. E2-specific binding and Ca2+ transport was monitored. At physiological E2 concentrations (0.1-1.5 nmol/L), specific E2 binding to mitochondria isolated from hippocampal synaptosomes was detected with a B-max and K-m of 37.6 +/- 2.6 fmol/mg protein and 0.69 +/- 0.14 nmol/L of free E2, respectively. The main mitochondrial Ca2+ influx mechanism is the Ruthenium Red-sensitive uniporter driven by mitochondrial membrane potential. Despite no effect of E2 on Ca2+ influx, a physiological E2 concentration (0.5 nmol/L) protected mitochondrial membrane potential and consequently Ca2+ influx from the uncoupling agent carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (1 mu mol/L). In neuronal cells the predominant mitochondria! Ca2+ efflux mechanism is the Na+/Ca2+ exchanger. E2 caused Ca2+ efflux inhibition (by 46%) coupled with increased affinity of the Na+/Ca2+ exchanger for Na+. Using E2 receptor (ER alpha and ER beta) antagonists and agonists, we confirmed ER betas involvement in E2-induced mitochondrial membrane potential protection as well as Ca2+ efflux inhibition. In summary, our results indicate that the nongenomic neuromodulatory role of E2 in rat hippocampus is achieved by affecting mitochondria! Ca2+ transport via, in part, mitochondrial ER beta. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.", journal = "Neuroscience", title = "Inhibition of Mitochondrial Na+-Dependent Ca2+ Efflux By 17 Beta-Estradiol in the Rat Hippocampus", volume = "192", pages = "195-204", doi = "10.1016/j.neuroscience.2011.06.030" }
Petrović, S., Velickovic, N., Stanojević, I., Milošević, M., Drakulić, D. R., Stanojlović, M. R.,& Horvat, A.. (2011). Inhibition of Mitochondrial Na+-Dependent Ca2+ Efflux By 17 Beta-Estradiol in the Rat Hippocampus. in Neuroscience, 192, 195-204. https://doi.org/10.1016/j.neuroscience.2011.06.030
Petrović S, Velickovic N, Stanojević I, Milošević M, Drakulić DR, Stanojlović MR, Horvat A. Inhibition of Mitochondrial Na+-Dependent Ca2+ Efflux By 17 Beta-Estradiol in the Rat Hippocampus. in Neuroscience. 2011;192:195-204. doi:10.1016/j.neuroscience.2011.06.030 .
Petrović, S., Velickovic, N., Stanojević, Ivana, Milošević, Maja, Drakulić, Dunja R., Stanojlović, Miloš R., Horvat, Anica, "Inhibition of Mitochondrial Na+-Dependent Ca2+ Efflux By 17 Beta-Estradiol in the Rat Hippocampus" in Neuroscience, 192 (2011):195-204, https://doi.org/10.1016/j.neuroscience.2011.06.030 . .