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Comparative Effects of Alpha- and Gamma-Tocopherol on Mitochondrial Functions in Alzheimer's Disease In Vitro Model.

ABSTRACT: Vitamin E acts as an antioxidant and reduces the level of reactive oxygen species (ROS) in Alzheimer's disease (AD). Alpha-tocopherol (ATF) is the most widely studied form of vitamin E besides gamma-tocopherol (GTF) which also shows beneficial effects in AD. The levels of amyloid-beta (A?) and amyloid precursor protein (APP) increased in the brains of AD patients, and mutations in the APP gene are known to enhance the production of A?. Mitochondrial function was shown to be affected by the increased level of A? and may induce cell death. Here, we aimed to compare the effects of ATF and GTF on their ability to reduce A? level, modulate mitochondrial function and reduce the apoptosis marker in SH-SY5Y cells stably transfected with the wild-type or mutant form of the APP gene. The A? level was measured by ELISA, the mitochondrial ROS and ATP level were quantified by fluorescence and luciferase assay respectively whereas the complex V enzyme activity was measured by spectrophotometry. The expressions of genes involved in the regulation of mitochondrial membrane permeability such as voltage dependent anion channel (VDAC1), adenine nucleotide translocase (ANT), and cyclophilin D (CYPD) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), while the expressions of cyclophilin D (CypD), cytochrome c, Bcl2 associated X (BAX), B cell lymphoma-2 (Bcl-2), and pro-caspase-3 were determined by western blot. Our results showed that mitochondrial ROS level was elevated accompanied by decreased ATP level and complex V enzyme activity in SH-SY5Y cells expressing the mutant APP gene (p?

SUBMITTER: Pahrudin Arrozi A

PROVIDER: S-EPMC7265356 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Comparative Effects of Alpha- and Gamma-Tocopherol on Mitochondrial Functions in Alzheimer's Disease In Vitro Model.

Pahrudin Arrozi Aslina A Shukri Siti Nur Syazwani SNS Wan Ngah Wan Zurinah WZ Mohd Yusof Yasmin Anum YA Ahmad Damanhuri Mohd Hanafi MH Jaafar Faizul F Makpol Suzana S

Scientific reports 20200602 1

Vitamin E acts as an antioxidant and reduces the level of reactive oxygen species (ROS) in Alzheimer's disease (AD). Alpha-tocopherol (ATF) is the most widely studied form of vitamin E besides gamma-tocopherol (GTF) which also shows beneficial effects in AD. The levels of amyloid-beta (Aβ) and amyloid precursor protein (APP) increased in the brains of AD patients, and mutations in the APP gene are known to enhance the production of Aβ. Mitochondrial function was shown to be affected by the incre ...[more]

PMID: 32488024

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Project description:BackgroundTocopherol isoforms may regulate child lung growth and spirometric measures.ObjectiveOur aim was to determine the extent to which plasma α-tocopherol (α-T) or γ-tocopherol (γ-T) isoform levels in early childhood or in utero are associated with childhood lung function.MethodsWe included 622 participants in the Project Viva cohort who had lung function at a mid-childhood visit (age 6-10 years). Maternal and child tocopherol isoform levels were measured by HPLC at the second trimester and 3 years of age, respectively. Multivariable linear regression models (adjusted for mid-childhood body mass index z scores, maternal education, smoking in pregnancy, and prenatal particulate matter with diameter of <2.5 micrometers (PM2.5) particulate exposure) stratified by tertiles of child γ-T level were used to assess the association of α-T levels with FEV1 and forced vital capacity (FVC) percent predicted. Similarly, models stratified by child α-T tertile evaluated associations of γ-T levels with lung function. We performed similar analyses with maternal second trimester tocopherol isoform levels.ResultsThe median maternal second trimester α-T level was 63 μM (interquartile range = 47-82). The median early-childhood level was 25 μM (interquartile range = 20-33 μM). In the lowest tertile of early-childhood γ-T, children with a higher α-T level (per 10 μM) had a higher mid-childhood FEV1 percent predicted (β = 3.09; 95% CI = 0.58-5.59 and a higher FVC percent predicted (β = 2.77; 95% CI = 0.47-5.06). This protective association of α-T was lost at higher γ-T levels. We did not see any consistent associations of second trimester levels of either α-T or γ-T with mid-childhood FEV1 or FVC.ConclusionWhen γ-T levels were in the lowest tertile, a higher early-childhood α-T level was associated with better lung function at mid-childhood. Second trimester maternal plasma α-T concentration was 3-fold higher than in the adult nonpregnant female population.

Dataset Information

Comparative Effects of Alpha- and Gamma-Tocopherol on Mitochondrial Functions in Alzheimer's Disease In Vitro Model.

Publications

Comparative Effects of Alpha- and Gamma-Tocopherol on Mitochondrial Functions in Alzheimer's Disease In Vitro Model.

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