D-Amino-acid oxidase is involved in D-serine-induced nephrotoxicity
D-Amino-acid oxidase is involved in D-serine-induced nephrotoxicity
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DOI：
10.1021/tx0500326
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发表时间：
2005-11-01
影响因子：
4.1
通讯作者：
Konno, R
中科院分区：
文献类型：
--
作者：
Maekawa, M;Okamura, T;Konno, R
D-丝氨酸对大鼠具有肾毒性。根据间接证据，怀疑D-氨基酸氧化酶参与了这种肾毒性。由于我们发现莱亚/SENDAI大鼠缺乏D-氨基酸氧化酶，我们使用莱亚/SENDAI大鼠和对照F344大鼠检测该酶是否与D-丝氨酸诱导的肾毒性相关。当将已知通过D-氨基酸氧化酶代谢具有肾毒性作用的D-炔丙基甘氨酸腹膜内注射到F344大鼠中时，其引起糖尿和多尿。然而，D-炔丙基甘氨酸注射到莱亚/SENDAI大鼠中没有引起任何糖尿或多尿，表明D-氨基酸氧化酶在这些大鼠中肯定没有功能。然后将D-丝氨酸注射到F344和莱亚/SENDAI大鼠中。它在F344大鼠中引起糖尿和多尿，但在莱亚/SENDAI大鼠中不引起。这些结果清楚地表明，D-氨基酸氧化酶是负责D-丝氨酸诱导的肾毒性。
D-Serine is nephrotoxic in rats. Based on circumstantial evidence, it has been suspected that D-amino-acid oxidase is involved in this nephrotoxicity. Since we found that LEA/SENDAI rats lacked D-amino-acid oxidase, we examined whether this enzyme was associated with D-serine-induced nephrotoxicity using the LEA/SENDAI rats and control F344 rats. When D-propargylglycine, which is known to have a nephrotoxic effect through its metabolism by D-amino-acid oxidase, was injected intraperitoneally into the F344 rats, it caused glucosuria and polyuria. However, injection of D-propargylglycine into LEA/SENDAI rats did not cause any glucosuria or polyuria, indicating that D-amino-acid oxidase is definitely not functional in these rats. D-Serine was then injected into the F344 and LEA/SENDAI rats. It caused glucosuria and polyuria in the F344 rats but not in the LEA/SENDAI rats. These results indicate clearly that D-amino-acid oxidase is responsible for the D-serine-induced nephrotoxicity.