Calcium Enhances In Vitro Free Radical‐Induced Damage to Brain Synaptosomes, Mitochondria, and Cultured Spinal Cord Neurons
Calcium Enhances In Vitro Free Radical‐Induced Damage to Brain Synaptosomes, Mitochondria, and Cultured Spinal Cord Neurons
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钙增强体外自由基对大脑突触体、线粒体和培养的脊髓神经元的损伤
DOI：
10.1111/j.1471-4159.1985.tb05555.x
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发表时间：
1985
影响因子：
4.7
通讯作者：
Tracey Goodman
中科院分区：
文献类型：
--
作者：
J. Braughler;L. Duncan;Tracey Goodman
摘要：在无钙Krebs缓冲液中，大鼠脑突触体与黄嘌呤和黄嘌呤氧化酶(X/XO)预孵育后，突触体对γ-氨基丁酸的摄取抑制了27%。加入1.5 mM CaCl2使X/XO的抑制率增加到46%，当加入钙离子载体A23187时，抑制作用基本完全。在其他研究中，纯化的大鼠脑线粒体与X/XO和4μM CaCl2一起预孵育后，以谷氨酸/苹果酸为底物的状态3呼吸显著减少(38%)，而单独使用X/XO或Ca~(2+)时未见此现象。用X/XO/ADP/FeCl2和A23187孵育培养的小鼠脊髓神经元也得到了类似的结果，通过神经元Na+，K+-ATPase活性降低32%来评估其膜损伤。X/XO/ADP/FeCl2和A23187单独都没有引起明显的抑制作用。这些结果证实了自由基和钙离子对膜功能的协同损伤作用。此外，他们认为，在体内完全或几乎完全缺血时，自由基致膜脂过氧化，当与细胞内钙离子增加相结合时，可能会导致强烈的细胞扰动。
Abstract: Preincubation of rat brain synaptosomes with xanthine and xanthine oxidase (X/XO) in Ca2+‐free Krebs buffer resulted in a 27% inhibition of synaptosomal γ‐aminobutyric acid (GABA) uptake. Addition of 1.5 mM CaCl2 increased the inhibition with X/XO to 46%, and inhibition was essentially complete when the calcium ionophore A23187 also was included. In other studies, preincubation of purified rat brain mitochondria with the combination of X/XO and 4 μM CaCl2 produced a significant (38%) decrease in state 3 respiration with glutamate/malate as substrate that was not seen with either X/XO or Ca2+ alone. Similar results were obtained using cultured mouse spinal cord neurons in which incubation with X/XO/ADP/FeCl2 and A23187 produced membrane damage as assessed by a 32% reduction of neuronal Na+, K+‐ATPase activity. Neither X/XO/ADP/FeCl2 nor A23187 alone caused detectable inhibition. These results demonstrate the synergistic damaging effect of free radicals and Ca2+ on membrane function. In addition, they suggest that free radical‐induced peroxidation of membrane lipid, occurring focally during complete or nearly complete ischemia in vivo, could result in intense cellular perturbation when coupled with increased intracellular Ca2+.
离子载体 A23187 对大鼠胸腺细胞钙摄取和细胞活力协调作用的假设机制。
DOI：
10.1016/0005-2736(82)90042-6
发表时间：
1982
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Segal,J;Ingbar,SH
通讯作者：
Ingbar,SH
疾病生物学：凝固性坏死发病机制中的膜损伤和钙稳态。
DOI：
--
发表时间：
1982
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Farber,JL
通讯作者：
Farber,JL