Taurine Ameliorates Impaired the Mitochondrial Function and Prevents Stroke-like Episodes in Patients with MELAS

Abstract

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 ResultsThe 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 strokelike episodes associated with MELAS.

Neuroprotective Mechanisms of Taurine against Ischemic Stroke

“…The decrease in intracellular: extracellular taurine ratio attenuates the protective role of taurine and could potentiate neuronal damage during ischemia. The administration of exogenous taurine protects the neuropile in ischemic stroke, evident from numerous experimental reports [23,63,65,69,70,73,140,141,142,144,154,155,156,160,176,179,190,206,207,208,209,210,212,217]. Exogenous taurine is able to elicit its neuroprotective mechanisms both at the intracellular and the extracellular level.…”

“…Rikimaru and colleagues using a culture system of MELAS patient-derived pathogenic cells reported that a high concentration of taurine (40 mM for 4 day exposure) was able to reverse the mitochondrial dysfunction observed in these patients. In their study, taurine increase the oxygen consumption rate, increased the Δψm in a time-dependent and dose-dependent (0 mM, 20 mM and 60 mM) manner and reduced oxidative stress [160]. The study also reported that the MRI of MELAS patients, treated with taurine, showed a reduction in the spread of the ischemic infarct to different brain region.…”

“…Recently Rikimaru and colleagues reported that the addition of taurine to the culture media of MELAS patient-derived cells ameliorated reduced oxygen consumption, improves the mitochondrial membrane potential and reduced oxidative stress [160]. In the same study Rikimaru and colleagues reported that taurine protected the brains of two MELAS patients from the spread of stroke-like lesions, revealed by MRI.…”

“…Taurine neuroprotective effects in these patients were manifested in an amelioration and eventually complete cessation of stroke-like episodes. In this small clinical study a daily dose of taurine (0.25 g/kg/day) was administered for over a period of nine years but protection was observed from the beginning of the study (year one) as seen from MRI of the brain and the alleviation of symptomatic stroke-like episodes [160]. Apart from this small study there seems to be no other clinical study on taurine in stroke patients.…”

Investigation of biomarkers of early taurine deficiency in Florida pompano Trachinotus carolinus

“…Contrarily, lack of this modification leads to errors in translation of proteins encoded by the mitochondrial genome. These include enzymes of the electron transport chain, the defect of which causes superoxide generation and the ensuing oxidative stress (Jong et al, 2012), as well as gives rise to mitochondrial encephalomyopathic diseases in mammals (Rikimaru et al, 2012;Umeda et al, 2005;Yasukawa et al, 2005). Since three of the COX subunits are encoded by the mitochondrial genome, the reductions in hepatic protein content (Fig.…”