Neurotoxic effects of dietary aluminium.
Neurotoxic effects of dietary aluminium.
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膳食铝的神经毒性作用。
DOI：
10.1002/9780470514306.ch15
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Johnson,GV
中科院分区：
文献类型：
--
作者：
Jope,RS;Johnson,GV
对大鼠长期口服铝的神经化学反应进行了研究。成年大鼠饮水中加入0.3%铝4周或更长时间，断奶大鼠给予8周铝。成年大鼠出现选择性认知功能障碍。铝抑制钙离子流动和磷脂酰肌醇代谢，其产物1，4，5-三磷酸调节细胞内钙离子水平。在断奶大鼠中，铝降低了海马区肌醇1，4，5-三磷酸的活体浓度。在成年和断奶大鼠的不同脑区，cAMP浓度增加了30-70%。铝可促进激动剂刺激的环磷酸腺苷的产生，但不能促进基础环磷酸腺苷的产生。推测铝抑制了刺激性G蛋白Gs的GTP酶活性，导致刺激后GsR的激活时间延长和环磷酸腺苷的生成增加。铝处理还增加了微管相关蛋白2(MAP-2)和200 kDa神经丝蛋白(NF-H)的磷酸化，但对其他几种磷蛋白没有影响。用免疫印迹法检测MAP-2、tau、NF-H、NF-M(150 KDa)、NF-L(68 KDa)、微管蛋白和血影蛋白等7种结构蛋白在大鼠脑区的表达。MAP-2的下降最为稳定。这些研究表明，长期口服铝对大鼠有显著的神经化学后果。涉及三个作用部位：钙稳态改变，环磷酸腺苷生成增加，以及细胞骨架蛋白磷酸化状态和浓度的变化。
Neurochemical responses to chronic oral aluminium administration have been studied in rats. Aluminium (0.3%) was added to drinking water of adult rats for four weeks or longer and weanling rats were given aluminium for eight weeks. Selective cognitive impairment was demonstrated in the adult rats. Aluminium inhibited calcium flux and phosphoinositide metabolism, one product of which (inositol 1,4,5‐trisphosphate) modulates intracellular calcium levels. In weanling rats aluminium decreased thein vivoconcentration of inositol 1,4,5‐trisphosphate in the hippocampus. An increase in cyclic AMP concentrations by 30–70% in various brain regions in adult and weanling rats was found. Aluminium enhanced agonist‐stimulated but not basal cyclic AMP productionin vitro. It was postulated that aluminium inhibits the GTPase activity of the stimulatory G protein, Gs, leading to prolonged activation of Gsafter receptor stimulation and increased cyclic AMP production. Aluminium treatment also increased the phosphorylation of microtubule‐associated protein 2 (MAP‐2) and the 200 kDa neurofilament protein (NF‐H) but several other phosphoproteins were unaffected. Concentrations of seven structural proteins—MAP‐2, tau, NF‐H, NF‐M (150 kDa), NF‐L (68 kDa), tubulin and spectrin‐were measured in rat brain regions by immunoblot methods. MAP‐2 was most consistently decreased.These studies show that chronic oral aluminium administration to rats has significant neurochemical consequences. Three sites of action are implicated: altered calcium homeostasis, enhanced cyclic AMP production, and changes in cytoskeletal protein phosphorylation states and concentrations.
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铝螯合剂（转铁蛋白）可逆转阿尔茨海默病大脑制剂中的生化缺陷
DOI：
--
发表时间：
1989
期刊：
The Lancet
影响因子：
--
作者：
J. Cowburn;J. Blair
通讯作者：
J. Blair
氟化物和铝抑制转导蛋白 GTP 酶活性的机制。
影响因子：
4.8
作者：
Y. Kanaho;J. Moss;M. Vaughan
通讯作者：
M. Vaughan
铝可增加大鼠体内大脑皮层的环磷酸腺苷。
影响因子：
6.1
作者：
Johnson,GV;Jope,RS
通讯作者：
Jope,RS
影响因子：
11.4
作者：
PAI, EF;KRENGEL, U;WITTINGHOFER, A
通讯作者：
WITTINGHOFER, A
影响因子：
56.9
作者：
T. L. Macdonald;W. Humphreys;R. B. Martin
通讯作者：
T. L. Macdonald;W. Humphreys;R. B. Martin