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首页> 外文期刊>Biochemistry >Arachidonic Acid Enhances Intracellular [Ca2+]_i Increase and Mitochondrial Depolarization Induced by Glutamate in Cerebellar Granule Cells
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Arachidonic Acid Enhances Intracellular [Ca2+]_i Increase and Mitochondrial Depolarization Induced by Glutamate in Cerebellar Granule Cells

机译：花生四烯酸增强谷氨酸在小脑颗粒细胞中诱导的细胞内[Ca2 +] _ i增加和线粒体去极化

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Maturation of primary neuronal cultures is accompanied by an increase in the proportion of cells that exhibit biphasic increase in free cytoplasmic Ca2+([Ca2+]i) followed by synchronic decrease in electrical potential difference across the inner mitochondrial membrane (DELTA PSI_m) in response to stimulation of glutamate receptors.In the present study we have examined whether the appearance of the second phase of [Ca2+];change can be attributed to arachidonic acid (AA) release in response to the effect of glutamate (Glu) on neurons.Using primary culture of rat cerebellar granule cells we have investigated the effect of AA (1-20 uM) on [Ca2+]_i DELTA PSI_m,and [ATP] and changes in these parameters induced by neurotoxic concentrations of Glu (100 uM,10-40 min).At <=10 uM,AA caused insignificant decrease in DELTA PSI_m without any influence on [Ca2+]_i.The mitochondrial ATPase inhibitor oligomycin enhanced AA-induced decrease in DELTA PSI_M;this suggests that AA may inhibit mitochondrial respiration.Addition of AA during the treatment with Glu resulted in more pronounced augmentation of [Ca2+]_i and the decrease in DELTA PSI_m than the changes in these parameters observed during independent action of AA;removal of Glu did not abolish these changes.An inhibitor of the cyclooxygenase and lipoxygenase pathways of AA metabolism,5,8,11,14-eicosatetraynoic acid,increased the proportion of neurons characterized by Glu-induced biphasic increase in [Ca2+]_i and the decrease in DELTA PSI_m.Palmitic acid (30 uM) did not increase the percentage of neurons exhibiting biphasic response to Glu.Co-administration of AA and Glu caused 2-3 times more pronounced decrease in ATP concentrations than that observed during the independent effect of AA and Glu.The data suggest that AA may influence the functional state of mitochondria,and these changes may promote biphasic [Ca2+]_i and DELTA PSI_m responses of neurons to the neurotoxic effect of Glu.
机译：原代神经元培养物的成熟伴随着游离胞质Ca2 +（[Ca2 +] i）呈两相增加的细胞比例增加，随后线粒体内膜电位差随刺激而同步降低在本研究中，我们研究了[Ca2 +]第二相的出现是否可归因于响应于谷氨酸（Glu）对神经元的影响的花生四烯酸（AA）的释放。在大鼠小脑颗粒细胞中，我们研究了AA（1-20 uM）对[Ca2 +] _ i DELTA PSI_m和[ATP]的影响，以及神经毒性浓度的Glu（100 uM，10-40 min）诱导的这些参数的变化在<= 10 uM时，AA导致DELTA PSI_m的降低不显着，而对[Ca2 +] _ i没有任何影响。线粒体ATPase抑制剂寡霉素增强了AA诱导的DELTA PSI_M的降低;这表明AA可能抑制了线粒体与在AA的独立作用期间观察到的这些参数的变化相比，在用Glu治疗的过程中添加AA导致[Ca2 +] _ i的增加更明显，而DELTA PSI_m的降低更明显;去除Glu并不能消除这些变化。酸，5,8,11,14-二十碳四丁酸的AA代谢的环氧合酶和脂氧合酶途径的增加，增加了以Glu诱导的[Ca2 +] _ i双相增加和DELTA PSI_m的双相减少为特征的神经元的比例。棕榈酸（30 uM ）并没有增加对Glu表现出双相反应的神经元的百分比.AA和Glu的共同给药导致ATP浓度的降低是AA和Glu的独立作用期间观察到的2-3倍。影响线粒体的功能状态，这些变化可能促进神经元对Glu的神经毒性作用的双相[Ca2 +] _ i和DELTA PSI_m反应。

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