Taurine Ameliorates Impaired the Mitochondrial Function and Prevents Stroke-like Episodes in Patients with MELAS
Taurine Ameliorates Impaired the Mitochondrial Function and Prevents Stroke-like Episodes in Patients with MELAS
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DOI：
10.2169/internalmedicine.51.7529
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发表时间：
2012-01-01
影响因子：
1.2
通讯作者：
Sunada, Yoshihide
中科院分区：
文献类型：
--
作者：
Rikimaru, Mitsue;Ohsawa, Yutaka;Sunada, Yoshihide
目的肌病、脑病、乳酸中毒和卒中样发作(MELAS)患者A3243G突变型线粒体(Mt)tRNA(Leu(UUR))在第一反密码子(“Wobble”)核苷酸转录后牛磺酸修饰缺失。最近，tRNAs中的摆动核苷酸修饰被认为是准确和有效地破译密码子的重要因素。方法和结果牛磺酸可改善MELAS患者细胞的氧耗量，降低线粒体膜电位，增加氧化应激。此外，大剂量口服牛磺酸(0.25g/kg/d)在9年多的时间内完全预防了2例MELAS患者的卒中样发作。结论补充牛磺酸可能是预防MELAS相关卒中样发作的一种新的潜在治疗方案。
Objective Post-transcriptional taurine modification at the first anticodon ("wobble") nucleotide is deficient in A3243G-mutant mitochondrial (mt) tRNA(Leu(UUR)) of patients with myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Wobble nucleotide modifications in tRNAs have recently been identified to be important in the accurate and efficient deciphering of codons. We herein examined whether taurine can alleviate mitochondrial dysfunction in patient-derived pathogenic cells and prevent clinical symptoms in MELAS patients.Methods and Results The addition of taurine to the culture media ameliorated the reduced oxygen consumption, decreased the mitochondrial membrane potential, and increased the oxidative stress in MELAS patient-derived cells. Moreover, high dose oral administration of taurine (0.25 g/kg/day) completely prevented stroke-like episodes in two MELAS patients for more than nine years.Conclusion Taurine supplementation may be a novel potential treatment option for preventing the stroke-like episodes associated with MELAS.