Changes in mitochondrial NAD(P)H and glutamate-induced delayed calcium deregulation in cultured rat cerebellar granule neurons

被引：1

作者：

Surin A.M. ^{[1
]}

Zobova S.N. ^{[1
,3
]}

Tukhbatova G.R. ^{[2
]}

Senilova Y.E. ^{[2
]}

Pinelis V.G. ^{[2
]}

Khodorov B.I. ^{[1
]}

机构：

[1] Institute of General Pathology and Patophysiology, Russian Academy of Medical Sciences, Moscow 125315, Baltiyskaya ul.

[2] Scientific Centre for Children Health, Russian Academy of Medical Sciences, Moscow 119911, Lomonosovsky prosp.

[3] Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Partizan Zheleznyak ul.

来源：

Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology | 2010年 / 4卷 / 1期

基金：

俄罗斯基础研究基金会;

关键词：

Delayed calcium deregulation; Glutamate; Mitochondria; NAD(P)H; Neurons;

D O I：

10.1134/S1990747810010058

中图分类号：

学科分类号：

摘要：

Changes in cytosolic [Ca2+]i, mitochondrial potential (ΔVm), and mitochondrial NAD(P)H autofluorescence were compared in experiments on cultured cerebellar granule cells co-loaded with Ca2+ indicator Fluo-3FF or mitochondrial potential-sensitive probe Rh123. In the majority of neurons (94% of cells, n = 205, 28 experiments) the delayed Ca 2+ deregulation (DCD) induced by Glu (100 μM) was preceded by more or less prolonged decrease in NAD(P)H, which in 57% of cells underwent a further (secondary) reduction during DCD development. To clarify the origin of these changes in NAD(P)H production during DCD we examined the effects of the protonophore FCCP on NAD(P)H increase induced by the electron chain blocker CN (3 mM) application. The data suggest that a pronounced lowering of mitochondrial pH during DCD contributed to the mechanism of Glu-induced suppression of NAD(P)H production. © 2010 Pleiades Publishing, Ltd.

引用

页码：32 / 37

页数：5

共 14 条

[1]

Nicholls D.G., Vesce S., Kirk L., Chalmers S., Interactions between mitochondrial bioenegetics and cytoplasmic calcium in cultured cerebellar granule cells, Cell Calcium, 34, 4-5, pp. 407-424, (2003)

[2]

Khodorov B., Glutamate-induced deregulation of calcium homeostasis and mitochondrial dysfunction in mammalian central neurones, Progress in Biophysics and Molecular Biology, 86, 2, pp. 279-351, (2004)

[3]

Abramov A.Y., Duchen M.R., Mechanisms underlying the loss of mitochondrial membrane potential in glutamate excitotoxicity, Biochim. Biophys. Acta, 1777, pp. 953-964, (2008)

[4]

Khodorov B.I., Storozhevykh T.P., Surin A.M., Iuriavichus A.I., Sorokina E.G., Borodin A.V., Vinskaia N.P., Khaspekov L.G., Pinelis V.G., The leading role of mitochondrial depolarization in the mechanism of glutamate-induced disorder in Ca2+-homeostasis, Fiziol. Zh. Im. I. M. Sechenova, 87, 4, pp. 459-467, (2001)

[5]

Surin A.M., Bolshakov A.P., Mikhailova M.M., Sorokina E.G., Senilova Ya.E., Pinelis V.G., Khodorov B.I., Arachidonic acid enhances intracellular [Ca2+]i increase and mitochondrial depolarization induced by glutamate in cerebellar granule cells, Biochemistry (Moscow), 71, 8, pp. 864-870, (2006)

[6]

Duchen M.R., Surin A., Jacobson J., Imaging mitochondrial function in intact cells, Methods in Enzymology, 361, pp. 353-389, (2003)

[7]

Jekabsons M.B., Nicholls D.G., In Situ respiration and bioenergetic status of mitochondria in primary cerebellar granule neuronal cultures exposed continuously to glutamate, Journal of Biological Chemistry, 279, 31, pp. 32989-33000, (2004)

[8]

McCormack J.G., Denton R.M., Mitochondrial Ca2+ transport and the role of intramitochondrial Ca2+ in the regulation of energy metabolism, Dev. Neurosci., 15, pp. 165-173, (1993)

[9]

Lai J.C., Cooper A.J., Brain α-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors, J. Neurochem., 47, pp. 1376-1386, (1986)

[10]

Hartley Z., Dubinsky J.M., Changes in intracellular ph associated with glutamate excitotoxicity, J. Neurosci., 13, pp. 4690-4699, (1993)

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