کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10958032 | 1099952 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Levels of 5-methyltetrahydrofolate and ascorbic acid in cerebrospinal fluid are correlated: Implications for the accelerated degradation of folate by reactive oxygen species
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Deficiency of 5-methyltetrahydrofolate (5-MTHF) in cerebrospinal fluid (CSF) is associated with a number of neurometabolic conditions including mitochondrial electron transport chain defects. Whilst failure of the active transport of 5-methyltetrahydrofolate (5-MTHF) into the CSF compartment has been proposed as a potential mechanism responsible for the 5-MTHF deficiency seen in mitochondrial disorders, it is becoming increasingly clear that other mechanisms are involved. Here, we have considered the role of oxidative stress as a contributing mechanism. Concerning, ascorbic acid (AA), we have established a CSF reference range (103-303 μM) and demonstrated a significant positive correlation between 5-MTHF and AA. Furthermore, CSF itself was also shown to convey antioxidant properties towards 5-MTHF. However, this protection could be overcome by the introduction of a hydroxyl radical generating system. Using a neuronal model system, inhibition of mitochondrial complex I, by 58%, was associated with a 23% increase in superoxide generation and a significantly increased loss of 5-MTHF from the extracellular medium. Addition of AA (150 μM) was able to prevent this increased 5-MTHF catabolism. We conclude that increased generation of reactive oxygen species and/or loss of CSF antioxidants are also factors to consider with regard to the development of a central 5-MTHF deficiency. Co-supplementation of AA together with appropriate folate replacement may be of therapeutic benefit.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 63, Issue 8, December 2013, Pages 750-755
Journal: Neurochemistry International - Volume 63, Issue 8, December 2013, Pages 750-755
نویسندگان
Sophie-Beth Aylett, Viruna Neergheen, Iain P. Hargreaves, Simon Eaton, John M. Land, Shamima Rahman, Simon J.R. Heales,