Effect of neurotrophin-3 precursor on glutamate-induced calcium homeostasis deregulation in rat cerebellum granule cells.
Neurotrophin-3 (NT-3) belongs to the family of highly conserved dimeric growth factors that controls the differentiation and activity of various neuronal populations. Mammals contain both the mature (NT-3) and the precursor (pro-NT-3) forms of neurotrophin. Members of the neurotrophin family are involved in the regulation of calcium homeostasis in neurons; however, the role of NT-3 and pro-NT-3 in this process remains unclear. The current study explores the effects of NT-3 and pro-NT-3 on disturbed calcium homeostasis and decline of mitochondrial potential induced by a neurotoxic concentration of glutamate (Glu; 100 µM) in the primary culture of rat cerebellar granule cells. In this Glu excitotoxicity model, mature NT-3 had no effect on the induced changes in Ca²⁺ homeostasis. In contrast, pro-NT-3 decreased the period of delayed calcium deregulation (DCD) and concurrent strong mitochondrial depolarization. According to the amplitude of the increase in the intracellular free Ca²⁺ concentration ([Ca²⁺]i ) and Fura-2 fluorescence quenching by Mn²⁺ within the first 20 sec of exposure to Glu, pro-NT-3 had no effect on the initial rate of Ca²⁺ entry into neurons. During the lag period preceding DCD, the mean amplitude of [Ca²⁺]i rise was 1.2-fold greater in the presence of pro-NT-3 than in the presence of Glu alone (1.67 ±  0.07 and 1.39 ± 0.04, respectively, P < 0.05). The Glu-induced changes in Са²⁺ homeostasis in the presence of pro-NT-3 likely are due to the decreased rate of Са²⁺ removal from the cytosol during the DCD latency period.
Laboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia.
Dina R
DR
Safina
Laboratory of Ionic Transport and Intracellular Signaling Pathology, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia.|Laboratory of Molecular, Genetic, and Cell Biology, Scientific Center for Children's Health, Russian Academy of Medical Sciences, Moscow, Russia.|Laboratory of Electrophysiology, Pirogov Russian National Research Medical University, Moscow, Russia.
Alexander M
AM
Surin
Laboratory of Molecular, Genetic, and Cell Biology, Scientific Center for Children's Health, Russian Academy of Medical Sciences, Moscow, Russia.
Vsevolod G
VG
Pinelis
Laboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia.|Centre for Convergence of Nano-, Bio-, Information, and Cognitive Sciences and Technologies, National Research Centre "Kurchatov Institute,", Moscow, Russia.
Sergey V
SV
Kostrov
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D018698:Glutamic Acid / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D009474:Neurons / Q000187:drug effects*; D020933:Neurotrophin 3 / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats
D020933:Neurotrophin 3; D011498:Protein Precursors; D018698:Glutamic Acid; D002118:Calcium
calcium homeostasis; glutamate excitotoxicity; neurons; neurotrophins; proneurotrophins