Identification of zebrafish A2 adenosine receptors and expression in developing embryos.
Identification of zebrafish A2 adenosine receptors and expression in developing embryos.
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DOI：
10.1016/j.gep.2008.11.006
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Levenson R
中科院分区：
文献类型：
--
作者：
Boehmler W;Petko J;Woll M;Frey C;Thisse B;Thisse C;Canfield VA;Levenson R
A2A 腺苷受体 (AdR) 亚型已成为改善帕金森病 (PD) 治疗的一个有吸引力的靶点。本报告重点关注斑马鱼 a2 AdR 的表征。通过挖掘斑马鱼EST和基因组序列数据库，我们鉴定了斑马鱼的两个a2a（adora2a.1和adora2a.2）基因和一个a2b（adora2b）AdR基因。序列比较表明，预测的斑马鱼 A2 AdR 多肽与哺乳动物 A2 AdR 具有 62-74% 的氨基酸同一性。我们将 adora2a.1 基因定位到 8 号染色体，将 adora2a.2 基因定位到 21 号染色体，将 adora2b 基因定位到 5 号染色体。整体原位杂交分析表明斑马鱼 a2 AdR 基因主要在中枢神经系统 (CNS) 内表达。已知斑马鱼对 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 敏感，这是一种神经毒素，会导致人类和动物模型中的多巴胺能神经元选择性丧失和 PD 样症状。在这里，我们证明咖啡因（一种 A2A AdR 拮抗剂）对斑马鱼胚胎具有神经保护作用，抵抗 MPTP 的不利影响。这些结果表明，斑马鱼 AdR 可能作为测试 PD 治疗新治疗策略的有用靶标。
The A2A adenosine receptor (AdR) subtype has emerged as an attractive target in the pursuit of improved therapy for Parkinson’s disease (PD). This report focuses on characterization of zebrafish a2 AdRs. By mining the zebrafish EST and genomic sequence databases, we identified two zebrafish a2a (adora2a.1 and adora2a.2) genes and one a2b (adora2b) AdR gene. Sequence comparisons indicate that the predicted zebrafish A2 AdR polypeptides share 62–74% amino acid identity to mammalian A2 AdRs. We mapped the adora2a.1 gene to chromosome 8, the adora2a.2 gene to chromosome 21, and the adora2b gene to chromosome 5. Whole mount in situ hybridization analysis indicates zebrafish a2 AdR genes are expressed primarily within the central nervous system (CNS). Zebrafish are known to be sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that causes selective loss of dopaminergic neurons and PD-like symptoms in humans as well as in animal models. Here we show that caffeine, an A2A AdR antagonist, is neuroprotective against the adverse effects of MPTP in zebrafish embryos. These results suggest that zebrafish AdRs may serve as useful targets for testing novel therapeutic strategies for the treatment of PD.
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影响因子：
56.9
作者：
FITCH, WM;MARGOLIASH, E
通讯作者：
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作者：
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