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过表达人鸟氨酸脱羧酶基因的转基因小鼠大脑中能量代谢、细胞内pH值及游离镁离子浓度的核磁共振波谱研究

Nuclear magnetic resonance spectroscopy study on energy metabolism, intracellular pH, and free Mg2+ concentration in the brain of transgenic mice overexpressing human ornithine decarboxylase gene.

作者信息

Kauppinen R A, Halmekytö M, Alhonen L, Jänne J

机构信息

Department of Biochemistry and Biotechnology, University of Kuopio, Finland.

出版信息

J Neurochem. 1992 Mar;58(3):831-6. doi: 10.1111/j.1471-4159.1992.tb09332.x.

DOI:10.1111/j.1471-4159.1992.tb09332.x
PMID:1737994
Abstract

We have generated a transgenic mouse line strikingly overexpressing the human ornithine decarboxylase (ODC) gene in their brain. Brain ODC activity was increased in the transgenic animals by a factor of 70 in comparison with their nontransgenic littermates. The content of brain putrescine, the product of ODC, was greater than 60 mumol/g of tissue in the transgenic mice, whereas in the normal animals it was below the level that could be detected by an HPLC method. The concentrations of the higher polyamines (spermidine and spermine) were not significantly different from control values. 31P nuclear magnetic resonance (31P NMR) spectroscopy analyses revealed a significantly reduced (40%) free Mg2+ concentration as calculated from the chemical shift differences of the nucleoside triphosphate alpha and beta peaks in the brains of the transgenic animals. The lower free Mg2+ concentration in the brains of ODC transgenic mice was not a consequence of altered intracellular pH or changes in cellular high-energy metabolites. 1H NMR showed no differences in brain choline/N-acetylaspartate and total creatine/N-acetylaspartate ratios between the two animal groups. These ODC transgenic animals may serve as models in vivo for studies on cerebral postischemic events and on epilepsy, as polyamines are supposed to be involved in these processes.

摘要

我们已经培育出一种转基因小鼠品系,其大脑中显著过表达人类鸟氨酸脱羧酶(ODC)基因。与非转基因同窝小鼠相比,转基因动物大脑中的ODC活性增加了70倍。ODC产物腐胺在转基因小鼠脑组织中的含量大于60 μmol/g,而在正常动物中,其含量低于高效液相色谱法可检测的水平。高级多胺(亚精胺和精胺)的浓度与对照值无显著差异。31P核磁共振(31P NMR)光谱分析显示,根据转基因动物大脑中核苷三磷酸α和β峰的化学位移差异计算,游离Mg2+浓度显著降低(40%)。ODC转基因小鼠大脑中较低的游离Mg2+浓度并非细胞内pH值改变或细胞高能代谢产物变化的结果。1H NMR显示,两组动物大脑中胆碱/N-乙酰天冬氨酸和总肌酸/N-乙酰天冬氨酸的比值没有差异。这些ODC转基因动物可作为体内模型,用于研究脑缺血后事件和癫痫,因为多胺被认为参与了这些过程。

相似文献

1
Nuclear magnetic resonance spectroscopy study on energy metabolism, intracellular pH, and free Mg2+ concentration in the brain of transgenic mice overexpressing human ornithine decarboxylase gene.过表达人鸟氨酸脱羧酶基因的转基因小鼠大脑中能量代谢、细胞内pH值及游离镁离子浓度的核磁共振波谱研究
J Neurochem. 1992 Mar;58(3):831-6. doi: 10.1111/j.1471-4159.1992.tb09332.x.
2
Cerebral energy metabolism and immediate early gene induction following severe incomplete ischaemia in transgenic mice overexpressing the human ornithine decarboxylase gene: evidence that putrescine is not neurotoxic in vivo.过表达人鸟氨酸脱羧酶基因的转基因小鼠严重不完全缺血后脑能量代谢及即刻早期基因诱导:腐胺在体内无神经毒性的证据
Eur J Neurosci. 1995 Sep 1;7(9):1840-9. doi: 10.1111/j.1460-9568.1995.tb00704.x.
3
Concurrent overexpression of ornithine decarboxylase and spermidine/spermine N(1)-acetyltransferase further accelerates the catabolism of hepatic polyamines in transgenic mice.鸟氨酸脱羧酶和亚精胺/精胺N(1)-乙酰转移酶的同时过表达进一步加速了转基因小鼠肝脏多胺的分解代谢。
Biochem J. 2001 Sep 1;358(Pt 2):343-8. doi: 10.1042/0264-6021:3580343.
4
Transgenic mice over-producing putrescine in their tissues do not convert the diamine into higher polyamines.组织中过量产生腐胺的转基因小鼠不会将二胺转化为高级多胺。
Biochem J. 1993 Apr 15;291 ( Pt 2)(Pt 2):505-8. doi: 10.1042/bj2910505.
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Characterization of a transgenic mouse line over-expressing the human ornithine decarboxylase gene.一种过表达人鸟氨酸脱羧酶基因的转基因小鼠品系的特性分析。
Biochem J. 1991 Sep 15;278 ( Pt 3)(Pt 3):895-8. doi: 10.1042/bj2780895.
6
Neuroprotective role of ornithine decarboxylase activation in transient focal cerebral ischaemia: a study using ornithine decarboxylase-overexpressing transgenic rats.鸟氨酸脱羧酶激活在短暂性局灶性脑缺血中的神经保护作用:一项使用过表达鸟氨酸脱羧酶转基因大鼠的研究。
Eur J Neurosci. 1998 Jun;10(6):2046-55. doi: 10.1046/j.1460-9568.1998.00216.x.
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Transgenic mice overexpressing ornithine and S-adenosylmethionine decarboxylases maintain a physiological polyamine homoeostasis in their tissues.过表达鸟氨酸和S-腺苷甲硫氨酸脱羧酶的转基因小鼠在其组织中维持生理性多胺稳态。
Biochem J. 1997 Apr 15;323 ( Pt 2)(Pt 2):457-62. doi: 10.1042/bj3230457.
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Transgenic rats as models for studying the role of ornithine decarboxylase expression in permanent middle cerebral artery occlusion.转基因大鼠作为研究鸟氨酸脱羧酶表达在永久性大脑中动脉闭塞中作用的模型。
Stroke. 1997 Mar;28(3):639-45. doi: 10.1161/01.str.28.3.639.
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Long-term reduction of amplified ornithine decarboxylase sequences in human myeloma cells.人骨髓瘤细胞中扩增的鸟氨酸脱羧酶序列的长期减少。
Biochem J. 1995 Aug 15;310 ( Pt 1)(Pt 1):299-303. doi: 10.1042/bj3100299.
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Polyamine homeostasis in transgenic plants overexpressing ornithine decarboxylase includes ornithine limitation.过表达鸟氨酸脱羧酶的转基因植物中的多胺稳态包括鸟氨酸限制。
J Biochem. 2003 Nov;134(5):765-72. doi: 10.1093/jb/mvg205.

引用本文的文献

1
Physiological polyamines: simple primordial stress molecules.生理性多胺:简单的原始应激分子。
J Cell Mol Med. 2007 Jul-Aug;11(4):685-703. doi: 10.1111/j.1582-4934.2007.00077.x.
2
Endogenous ornithine in search for CNS functions and therapeutic applications.寻找中枢神经系统功能及治疗应用的内源性鸟氨酸。
Metab Brain Dis. 1993 Sep;8(3):151-79. doi: 10.1007/BF00996928.