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Defective methionine metabolism in the brain after repeated blast exposures might contribute to increased oxidative stress
Neurochemistry international ( IF 4.4 ) Pub Date : 2017-07-31 , DOI: 10.1016/j.neuint.2017.07.014
Peethambaran Arun , William B. Rittase , Donna M. Wilder , Ying Wang , Irene D. Gist , Joseph B. Long

Blast-induced traumatic brain injury (bTBI) is one of the major disabilities in Service Members returning from recent military operations. The neurobiological underpinnings of bTBI, which are associated with acute and chronic neuropathological and neurobehavioral deficits, are uncertain. Increased oxidative stress in the brain is reported to play a significant role promoting neuronal damage associated with both brain injury and neurodegenerative disorders. In this study, brains of rats exposed to repeated blasts in a shock tube underwent untargeted profiling of primary metabolism by automatic linear exchange/cold injection GC-TOF mass spectrometry and revealed acute and sub-acute disruptions in the metabolism of the essential amino acid methionine and associated antioxidants. Methionine sulfoxide, the oxidized metabolite of methionine, showed a sustained increase in the brain after blast exposure which was associated with a significant decrease in cysteine, the amino acid derived from methionine. Glutathione, the antioxidant synthesized from cysteine, also concomitantly decreased as did the antioxidant ascorbic acid. Reductions in ascorbic acid were accompanied by increased levels of its oxidized metabolite, dehydroascorbic acid and other metabolites such as threonic acid, isothreonic acid, glycolic acid and oxalic acid. Fluorometric analysis of the brains showed acute and sub-acute increase in total reactive oxygen species. In view of the fundamental importance of glutathione in the brain as an antioxidant, including its role in the reduction of dehydroascorbic acid to ascorbic acid, the disruptions in methionine metabolism elicited by blast exposure might prominently contribute to neuronal injury by promoting increased and sustained oxidative stress.



中文翻译:

反复爆炸暴露后脑中蛋氨酸代谢缺陷可能会导致氧化应激增加

爆炸引起的颅脑外伤(bTBI)是从最近的军事行动返回的服役人员中的主要残疾之一。与急性和慢性神经病理学和神经行为缺陷有关的bTBI的神经生物学基础尚不确定。据报道,大脑中增加的氧化应激在促进与脑损伤和神经退行性疾病相关的神经元损伤中起重要作用。在这项研究中,通过自动线性交换/冷注射GC-TOF质谱法对在电击管中反复遭受爆炸冲击的大鼠的大脑进行了主要代谢的非靶向分析,并揭示了必需氨基酸蛋氨酸的代谢中的急性和亚急性破坏和相关的抗氧化剂。甲硫氨酸亚砜,甲硫氨酸的氧化代谢产物,结果显示,爆炸冲击后大脑的持续增加与半胱氨酸(源自蛋氨酸的氨基酸)的显着减少有关。由半胱氨酸合成的抗氧化剂谷胱甘肽也随之减少,抗氧化剂抗坏血酸也随之减少。抗坏血酸的减少伴随着其氧化代谢产物,脱氢抗坏血酸和其他代谢产物(如苏糖酸,异苏糖酸,乙醇酸和草酸)水平的增加。大脑的荧光分析表明,总活性氧种类急剧增加和亚急性增加。鉴于谷胱甘肽在脑中作为抗氧化剂的根本重要性,包括其在将脱氢抗坏血酸还原为抗坏血酸中的作用,

更新日期:2017-07-31
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