The Subcellular Distribution of Alpha-Tocopherol in the Adult Primate Brain and Its Relationship with Membrane Arachidonic Acid and Its Oxidation Products.

Emily Mohn,Matthew Kuchan,Nirupa Matthan,Chung-Yen Chen,John Erdman,Martha Neuringer,Elizabeth Johnson

doi:10.3390/antiox6040097

Abstract

The relationship between α-tocopherol, a known antioxidant, and polyunsaturated fatty acid (PUFA) oxidation, has not been directly investigated in the primate brain. This study characterized the membrane distribution of α-tocopherol in brain regions and investigated the association between membrane α-tocopherol and PUFA content, as well as brain PUFA oxidation products. Nuclear, myelin, mitochondrial, and neuronal membranes were isolated using a density gradient from the prefrontal cortex (PFC), cerebellum (CER), striatum (ST), and hippocampus (HC) of adult rhesus monkeys (n = 9), fed a stock diet containing vitamin E (α-, γ-tocopherol intake: ~0.7 µmol/kg body weight/day, ~5 µmol/kg body weight/day, respectively). α-tocopherol, PUFAs, and PUFA oxidation products were measured using high performance liquid chromatography (HPLC), gas chromatography (GC) and liquid chromatography-gas chromatography/mass spectrometry (LC-GC/MS) respectively. α-Tocopherol (ng/mg protein) was highest in nuclear membranes (p < 0.05) for all regions except HC. In PFC and ST, arachidonic acid (AA, µg/mg protein) had a similar membrane distribution to α-tocopherol. Total α-tocopherol concentrations were inversely associated with AA oxidation products (isoprostanes) (p < 0.05), but not docosahexaenoic acid oxidation products (neuroprostanes). This study reports novel data on α-tocopherol accumulation in primate brain regions and membranes and provides evidence that α-tocopherol and AA are similarly distributed in PFC and ST membranes, which may reflect a protective effect of α-tocopherol against AA oxidation.

Highlights

Vitamin E is an essential, fat-soluble nutrient, obtained from nuts, oils, and green leafy vegetables [1]
It is possible that α-tocopherol maintains the integrity of cell membranes through inhibiting oxidation of polyunsaturated fatty acids (PUFA) [11], arachidonic acid (AA) and docosahexaenoic acid (DHA), the two major PUFAs found in the brain [12], and thereby combats the cell damage and neurodegeneration underlying cognitive impairment
Our findings indicate that, α-tocopherol accumulates in membranes, rich in both n-6 and n-3 PUFAs, it may be associated with preferentially protecting AA from oxidative damage

Summary

Introduction

Vitamin E is an essential, fat-soluble nutrient, obtained from nuts, oils, and green leafy vegetables [1]. Epidemiological studies have reported that lower tocopherol intake is associated with poorer cognitive function, compared to individuals with higher intakes [4], and reduced levels of α-tocopherol in plasma [5,6]. It is highly susceptible to ROS attacks on lipid, protein, and DNA [9]. This susceptibility is accentuated by the high concentrations of polyunsaturated fatty acids (PUFA) found in brain cell membranes. It is possible that α-tocopherol maintains the integrity of cell membranes through inhibiting oxidation of PUFAs [11], arachidonic acid (AA) and docosahexaenoic acid (DHA), the two major PUFAs found in the brain [12], and thereby combats the cell damage and neurodegeneration underlying cognitive impairment

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