Collapse of Neuronal Energy Balance As a Basis of L-Homocysteine Neurotoxicity
- 作者: Sitnikova L.1, Ivanova M.1, Stepanenko Y.1, Karelina T.1, Giniatullin R.2, Sibarov D.1, Abushik P.1, Antonov S.1
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隶属关系:
- Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
- University of Eastern Finland, Department of Neurobiology
- 期: 卷 12, 编号 4 (2018)
- 页面: 360-368
- 栏目: Articles
- URL: https://journals.rcsi.science/1990-7478/article/view/213328
- DOI: https://doi.org/10.1134/S1990747818050069
- ID: 213328
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详细
Using fluorescence detection methods, neurotoxic effects of L-homocysteine (HCY), L-glutamate (Glu), and N-methyl-D-aspartate (NMDA) on primary culture of rat cerebellar neurons were compared and the agonist-evoked intracellular Ca2+ responses and changes in mitochondrial membrane potential were studied. Long-term (5 h) action of HCY, Glu, or NMDA caused neuronal apoptosis and necrosis that was followed by a decrease of quantity of live cells to 40%. It was revealed using Fluo-3 that neurons differed by intracellular Ca2+ responses to 2-min applications of HCY. In response to all studied agonists, a brief peak or gradual increase of intracellular Ca2+ concentration was observed. Some neurons did not respond to HCY, but all responded to Glu and NMDA. A prolonged (60 min) treatment with agonists caused a rapid or delayed Ca2+ overload, while only a small portion of neurons were able to compensate the intracellular Ca2+ elevation. Six-minute applications of HCY or Glu to neurons induced similar changes of mitochondrial potential (φmit) measured by rhodamine123. In this protocol, the ability of the NMDA receptor agonists to cause the mitochondrial dysfunction could be arranged in the following order: NMDA > Glu = HCY. After a 60-min treatment the observed difference vanished because all of the agonists reduced φmit so that an uncoupling agent FCCP did not cause any additional changes in φmit. Thus, HCY-induced neurotoxicity in cerebellar neurons is comparable to that of Glu. In this feature cerebellar neurons differ from cortical neurons, in which HCY did not significantly change φmit during short-term application. This difference could be related with peculiarities of the HCY action on NMDA receptor subtypes expressed by cerebellar neurons.
作者简介
L. Sitnikova
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Email: antonov452002@yahoo.com
俄罗斯联邦, St. Petersburg, 194223
M. Ivanova
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Email: antonov452002@yahoo.com
俄罗斯联邦, St. Petersburg, 194223
Yu. Stepanenko
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Email: antonov452002@yahoo.com
俄罗斯联邦, St. Petersburg, 194223
T. Karelina
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Email: antonov452002@yahoo.com
俄罗斯联邦, St. Petersburg, 194223
R. Giniatullin
University of Eastern Finland, Department of Neurobiology
Email: antonov452002@yahoo.com
芬兰, Kuopio, P.O. Box 1627/Neulaniementie 2, 70211
D. Sibarov
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Email: antonov452002@yahoo.com
俄罗斯联邦, St. Petersburg, 194223
P. Abushik
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Email: antonov452002@yahoo.com
俄罗斯联邦, St. Petersburg, 194223
S. Antonov
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
编辑信件的主要联系方式.
Email: antonov452002@yahoo.com
俄罗斯联邦, St. Petersburg, 194223