CAFFEINE AND URIC ACID MEDIATE GLUTATHIONE SYNTHESIS FOR NEUROPROTECTION
CAFFEINE AND URIC ACID MEDIATE GLUTATHIONE SYNTHESIS FOR NEUROPROTECTION
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DOI：
10.1016/j.neuroscience.2011.02.047
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发表时间：
2011-05-05
期刊：
影响因子：
3.3
通讯作者：
Nakaki, T.
中科院分区：
文献类型：
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作者：
Aoyama, K.;Matsumura, N.;Nakaki, T.
多项流行病学研究表明，咖啡因摄入量和血浆尿酸（UA）水平与某些神经退行性疾病的发病率呈负相关。我们在这里报告一个新的机制，这些嘌呤衍生物增加神经元谷胱甘肽（GSH）的合成。腹腔注射咖啡因或UA到雄性C57 BL/6小鼠的海马中的总GSH水平显着增加。无论是SCH 58261，腺苷A2 A受体拮抗剂，也不是咯利普兰，磷酸二酯酶-4抑制剂，增加GSH水平。用别嘌呤醇（一种抑制尿酸生成的药物）预处理，没有改变咖啡因处理小鼠的GSH水平。在切片培养实验中，咖啡因或UA处理的海马CA 1锥体神经元对氧化剂暴露具有抵抗性。在SH-SY 5 Y细胞系的实验中，半胱氨酸摄取是钠依赖性的，与对照条件相比，咖啡因或UA预处理显著增加半胱氨酸摄取。海马切片培养实验也显示，咖啡因或UA处理后半胱氨酸和GSH含量增加。免疫组织化学分析显示，咖啡因或UA处理的小鼠海马兴奋性氨基酸载体-1（EAAC 1）阳性神经元中GSH水平增加。这些发现表明，嘌呤衍生物咖啡因和UA通过促进半胱氨酸摄取诱导神经元GSH合成，从而导致神经保护。(C)2011年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Several lines of epidemiological studies have indicated that caffeine consumption and plasma uric acid (UA) level were negatively correlated with the incidence of some neurodegenerative diseases. We report here a novel mechanism by which these purine derivatives increase neuronal glutathione (GSH) synthesis. Intraperitoneal injection of caffeine or UA into male C57BL/6 mice significantly increased total GSH levels in the hippocampus. Neither SCH58261, an adenosine A2A receptor antagonist, nor rolipram, a phosphodiesterase-4 inhibitor, increased GSH levels. Pretreatment with allopurinol, a drug to inhibit UA production, did not change the GSH level in the caffeine-treated mice. Hippocampal CA1 pyramidal neurons treated with caffeine or UA were resistant to oxidant exposure in the slice culture experiments. In experiments with the SH-SY5Y cell line, cysteine uptake was sodium-dependent and pretreatment with caffeine or UA increased cysteine uptake significantly as compared with the control conditions. Slice culture experiments using the hippocampus also showed increased cysteine and GSH contents after the treatment with caffeine or UA. Immunohistochemical analysis showed increased GSH levels in the hippocampal excitatory amino acid carrier-1 (EAAC1)-positive neurons of mice treated with caffeine or UA. These findings suggest that purine derivatives caffeine and UA induce neuronal GSH synthesis by promoting cysteine uptake, leading to neuroprotection. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.