Expression analysis of α-TTP, PI-TP and SPF genes in H₂O₂-induced HUVECs and neuronal cells supplemented with α-tocopherol and Tocotrienol-Rich Fraction

Vitamin E has 8 isoforms namely; α, β, γ, δ -tocopherols (TCP) and α, β, γ, δ -tocotrienols (TCT). Natural α-tocopherol (α-TCP) but not TCT is preferentially retained in the human body. Studies showed that α-tocopherol transfer protein (α-TTP) is responsible to bind α-TCP for cellular uptake. However, α-TTP has strong specificity and high affinity for α-TCP and poorly binds to α-tocotrienol. Despite of the nature of α-TTP discriminating tocotrienol, population with palm oil as primary source of lipid consisting of 75% TCT and 25% TCP which is taken daily, however has no alarming deficiency reported. Therefore, interest on mechanism of uptake of vitamin E is addressed in this study. The purposes of this study were to examine the modification of α-TTP together with other vitamin E binding related genes in regulating vitamin E uptake in neuronal cell and HUVECs under resting and oxidative stress. Oxidative stress was induced with H2O2 for one hour followed by supplementation with different ratios of α-TCP and Tocotrienol Rich Fraction (TRF) for 4 hours. Likewise, both cells were treated with vitamin E without oxidative stress. Real-time PCR was used to determine expression levels of the genes. The cellular levels of vitamin E were quantified by HPLC as the index of cell bioavailability. The study showed that expression levels of genes encoding the vitamin E binding proteins, including α-tocopherol transfer protein (α-TTP/TTPA), Supernatant protein factor (SPF/SEC14L2) and Phosphatidyl inositol transfer protein (PI-TP/PI-TPNA) in 0% α-TCP positively correlated to the cellular levels of vitamin E in resting neuronal cells and HUVECs under oxidative stress. The expression levels of all genes examined were different in the two cells under oxidative stress, which may contribute to cellular vitamin E content. However, in resting neuronal cells and HUVECs cells the levels were similar. Between the two cells, HUVECs was more sensitive to oxidative stress, which induced gene expressions of TTPA, SEC14L2, and PI-TPNA. Altogether, these results suggest that the regulation of TTPA, SEC14L2 and PI-TPNA genes in the HUVECs and the neurons, affects the distribution of vitamin E in endothelial and neuronal cells. Furthermore, it is reasonable to postulate that under conditions of oxidative stress, increased gene levels would cause increased α-TCP secretion from the neuronal cells or HUVECs thereby proteins could be modified and in the absence of α-TCP they may switch to take up TCT. Generally, our data suggests that probably the expression levels of vitamin E transport proteins might influence cellular concentrations of vitamin E levels in neuronal cells and HUVECs

Analysis of expression of vitamin E-binding proteins in H2O2 induced SK-N-SH neuronal cells supplemented with α-tocopherol and tocotrienol-rich fraction.

Natural α-tocopherol (α-TCP), but not tocotrienol, is preferentially retained in the human body. α-Tocopherol transfer protein (α-TTP) is responsible for binding α-TCP for cellular uptake and has high affinity and specificity for α-TCP but not α-tocotrienol. The purpose of this study was to examine the modification of α-TTP together with other related vitamin E-binding genes (i.e., TTPA, SEC14L2, and PI-TPNA) in regulating vitamin E uptake in neuronal cells at rest and under oxidative stress. Oxidative stress was induced with H2O2 for an hour which was followed by supplementation with different ratios of α-TCP and tocotrienol-rich fraction (TRF) for four hours. The cellular levels of vitamin E were quantified to determine bioavailability at cellular levels. The expression levels of TTPA, SEC14L2, and PI-TPNA genes in 0% α-TCP were found to be positively correlated with the levels of vitamin E in resting neuronal cells. In addition, the regulation of all the above-mentioned genes affect the distribution of vitamin E in the neuronal cells. It was observed that, increased levels of α-TCP secretion occur under oxidative stress. Thus, our results showed that in conclusion vitamin E-binding proteins may be modified in the absence of α-TCP to produce tocotrienols (TCT), as a source of vitamin E. The current study suggests that the expression levels of vitamin E transport proteins may influence the cellular concentrations of vitamin E levels in the neuronal cells

The Lancet Nigeria Commission: investing in health and the future of the nation.

Funder: Wellcome TrustHealth is central to the development of any country. Nigeria’s gross domestic product is the largest in Africa, but its per capita income of about ₦770 000 (US$2000) is low with a highly inequitable distribution of income, wealth, and therefore, health. It is a picture of poverty amidst plenty. Nigeria is both a wealthy country and a very poor one. About 40% of Nigerians live in poverty, in social conditions that create ill health, and with the ever-present risk of catastrophic expenditures from high out-of-pocket spending for health. Even compared with countries of similar income levels in Africa, Nigeria’s population health outcomes are poor, with national statistics masking drastic differences between rich and poor, urban and rural populations, and different regions