Brain γ-Tocopherol Levels Are Associated with Presynaptic Protein Levels in Elderly Human Midfrontal Cortex

Francisca A de Leeuw, William G Honer, Julie A Schneider, Martha Clare Morris

J Alzheimers Dis . 2020 Jul 25. doi: 10.3233/JAD-200166. Online ahead of print.

Abstract

Background: Higher vitamin E intake has been widely related to lower risks of cognitive decline and dementia. Animal models suggest that this relationship might be (partially) explained by the protection of vitamin E against presynaptic protein oxidation.

Objective: In this cross-sectional study, we aimed to examine the associations between brain tocopherols and presynaptic protein levels in elderly humans.

Methods: We examined associations of α- and γ-tocopherol brain levels with presynaptic protein levels in 113 deceased participants (age 88.5±6.0 years, 45 (40%) female) from the prospective Memory and Aging project. Three distinct presynaptic proteins, a SNARE protein composite, a synaptotagmin synaptophysin composite and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25), and syntaxin were measured in two cortical brain regions. Linear regression models assessed associations of brain tocopherols with presynaptic protein levels.

Results: Higher brain γ-tocopherol levels were associated with higher levels of the SNARE protein composite, complexin-I, complexin-II, the synaptotagmin synaptophysin composite, and septin-5 in the midfrontal cortex (B(SE) = 0.272 to 0.412 (0.084 to 0.091), p < 0.001 to 0.003). When additionally adjusted for global Alzheimer’s disease pathology, cerebral infarcts, and Lewy body disease pathology, these associations remained largely similar. No associations were found between α-tocopherol and presynaptic protein levels.

Conclusion: In this cross-sectional study, we found higher brain γ-tocopherol levels were associated with presynaptic protein levels in the midfrontal cortex. These results are consistent with a proposed role of vitamin E to maintain presynaptic protein levels.

Yuka Nakatsu, Shumpei Niida, Kiyoshi Tanaka, Shigeo Takenaka, Akiko Kuwabara

J Nutr Sci Vitaminol (Tokyo) . 2020;66(3):213-218. doi: 10.3177/jnsv.66.213.

Abstract

Since vitamin E is one of the most potent antioxidant and anti-inflammatory agents, vitamin E can play a role against arteriosclerosis through various actions. Then, we have studied the relationship between serum vitamin E status and risk factors for arteriosclerosis in Japanese postmenopausal women. One hundred and seven subjects (70.0±7.7 y) were evaluated for vitamin E status by measuring serum α- and γ-tocopherol (αT and γT) levels. The number of arteriosclerosis risk factors was defined by the existence of high blood pressure, hyperglycemia, and dyslipidemia. Median serum αT and γT concentrations were 24.32 and 2.79 μmol/L, respectively. In none of the subjects, serum αT level was below the cutoff value (<12 μmol/L) for vitamin E deficiency which causes fragile erythrocyte and hemolysis. While no significant differences were found in serum levels of αT and γT between the groups categorized by the number of arteriosclerosis risks, serum levels of αT adjusted by serum total cholesterol (TC) and triglyceride (TG) decreased with an increasing number of arteriosclerotic risk factors (p=0.074). Serum αT level adjusted by serum TC and TG was also a negative significant predictor for the number of arteriosclerosis risk factors controlled by covariates associated with arteriosclerosis. The present study described that serum vitamin E level was positively associated with a lower number of arteriosclerotic risks, and its role for preventing noncommunicable diseases was suggested.

William G Christen, Amy K Darke, John M Gaziano, Robert J Glynn, Phyllis J Goodman, Lori M Minasian, Ian M Thompson Jr

Acta Ophthalmol . 2020 Jul 23. doi: 10.1111/aos.14538. Online ahead of print.

Lettter to the Editor

Selenium and vitamin E are found in the human retina and retinal pigment epithelium and have been associated with risks of age-related macular degeneration (AMD) in observational epidemiological studies (Khoo et al. 2019). We examined a possible role for these nutrients in AMD prevention in the Select Eye Endpoints (SEE) Study, an ancillary study of the National Cancer Institute-sponsored Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized, placebo-controlled trial of selenium (200 lg/d) and/or vitamin E (400 IU/d) in prevention of prostate cancer among 35 533 apparently healthy men aged 50 years and older (Lippman et al. 2005; Lippman et al. 2009).

ADAM CHAPMAN

In a study published in the Tropical Life Sciences Research journal, researchers investigated the effect of tocotrienol supplementation on hair growth in volunteers suffering from hair loss. Twenty one volunteers were randomly assigned to orally receive 100 mg of mixed tocotrienols daily while 17 volunteers were assigned to receive placebo capsule orally. The volunteers were monitored for the number of hairs in a predetermined scalp area as well as the weight of 20 strands of one centimetre length hair clippings before supplementation, at four and eight months.

Magdalena M Olchawa, Grzegorz M Szewczyk, Andrzej C Zadlo, Olga I Krzysztynska-Kuleta, Tadeusz J Sarna

Pigment Cell Melanoma Res . 2020 Jul 23. doi: 10.1111/pcmr.12914. Online ahead of print.

Abstract

Aging may significantly modify antioxidant and photoprotective properties of melanin in retinal pigment epithelium (RPE). Here, photoreactivity of melanosomes (MS), isolated from younger and older human donors with and without added zeaxanthin and α-tocopherol, was analyzed by electron paramagnetic resonance oximetry, time-resolved singlet oxygen phosphorescence, and protein oxidation assay. The phototoxic potential of ingested melanosomes was examined in ARPE-19 cells exposed to blue light. Phagocytosis of FITC-labeled photoreceptor outer segments (POS) isolated from bovine retinas was determined by flow cytometry. Irradiation of cells fed MS induced significant inhibition of the specific phagocytosis with the effect being stronger for melanosomes from older than from younger human cohorts, and enrichment of the melanosomes with antioxidants reduced the inhibitory effect. Cellular protein photooxidation was more pronounced in samples containing older melanosomes, and it was diminished by antioxidants. This study suggests that blue light irradiated RPE melanosomes could induce substantial inhibition of the key function of the cells-their specific phagocytosis. The data indicate that while photoreactivity of MS and their phototoxic potential increase with age, they could be reduced by selected natural antioxidants.

Hong Sun, Jingli Yang, Xue Lin, Congfa Li, Yongjin He, Zhigang Cai, Guoyin Zhang, Hao Song

J Agric Food Chem . 2020 Jul 22;68(29):7710-7717. doi: 10.1021/acs.jafc.0c00294. Epub 2020 Jul 7.

Abstract

Delta-tocotrienol as a vitamin E isomer has received much attention because of its diverse biomedical applications. Microbial biosynthesis of delta-tocotrienol is a promising strategy for its economic and environmental advantages. Here, we accomplished complete biosynthesis of delta-tocotrienol in Saccharomyces cerevisiae from glucose. We first constructed and incorporated a heterologous pathway into the genome of S. cerevisiae by incorporating the genes hpd (from Pseudomonas putida KT2440), hpt (from Synechocystis sp. PCC 6803), and vte1 (from Arabidopsis thaliana) for the biosynthesis of delta-tocotrienol. We further enhanced the biosynthesis of the precursor geranylgeranyl diphosphate by overexpressing the thmg1 and ggppssa (from Sulfolobus acidocaldarius) genes, leading to a production titer of delta-tocotrienol of 1.39 ± 0.01 mg/L. Finally, we optimized the fermentation medium using the response surface methodology, enabling a high-titer production of delta-tocotrienol (3.56 ± 0.25 mg/L), ∼2.6-fold of that of the initial culture medium. Fed-batch fermentation in a 2 L fermenter was further used to enhance the production titer of delta-tocotrienol (4.10 ± 0.10 mg/L). To the best of our knowledge, this is the first report on the de novo biosynthesis of delta-tocotrienol in S. cerevisiae, and the highest titer obtained for microbial production of delta-tocotrienol.

Constantina Constantinou, Christiana Charalambous, Dimitrios Kanakis, Ourania Kolokotroni, Andreas I Constantinou

Nutr Cancer . 2020 Jul 22;1-7. doi: 10.1080/01635581.2020.1797128. Online ahead of print.

Abstract

The natural isoforms of vitamin E γ-tocotrienol (γ-ΤΤ) and δ-tocotrienol (δ-ΤΤ) and the synthetic derivative α-tocopheryl polyethylene glycol 1000 succinate (TPGS) have promising anticancer potency in a variety of cancer cell lines and animal models of cancer. Ongoing clinical trials are investigating the anti-tumor effectiveness of TTs in combination with chemotherapeutic agents in patients suffering from breast, colon, non-small cell lung and ovarian cancers. Despite extensive research on different types of cancer, the anticancer potency of TTs and TPGS has not been thoroughly investigated in leukemias. Given the fact that certain types of leukemias have very low survival rates and that patients suffer significantly from the toxic side effects of chemotherapeutic drugs, there is a need to develop novel treatments with increased specificity against cancer cells and reduced toxicity to the patients. The aim of this review is to report current evidence on the anticancer potency of TTs and TPGS on leukemic cells lines and to discuss future studies that could be carried out to investigate the role of these agents in the management of leukemias.

Xue Tan, Fangfang Zhong, Hongli Teng, Qingqing Li, Yitong Li, Zhinan Mei, Yu Chen, Guangzhong Yang

Fitoterapia . 2020 Jul 21;146:104688. doi: 10.1016/j.fitote.2020.104688. Online ahead of print.

Abstract

Three undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) and three tocotrienols derivatives, named as paucinochymol A-F (1-3 and 10-12), together with six known PPAPs, were isolated from the fruits of Garcinia paucinervis. Their structures and absolute configurations were determined by extensive NMR analysis and electronic circular dichroism (ECD) calculation methods. Paucinochymol A (1) is the first compound of this type featuring a ω-isogeranyl with tetrahydrofuran unit at C-1. Paucinochymols D and E (4-5) belong to rare tocotrienol with one glorious macrocyclic and an ortho-quinone moiety, respectively. The antiproliferative and anti-inflammatory activities of all isolates were tested. Four PPAPs exhibited weak inhibitory activities against three human cancer cell lines (HepG2, T98, MCF-7) with IC₅₀ values ranging from 10.0 to 16.0 μM. Paucinochymol D (10) displayed moderate inhibitory effects against nitric oxide (NO) production with the IC₅₀ value of 19.8 μM.

Maria Wallert, Lisa Börmel, Stefan Lorkowski

Mol Nutr Food Res . 2020 Jul 21;e2000097. doi: 10.1002/mnfr.202000097. Online ahead of print.

Abstract

Inflammation-driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease, and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, has been identified as a key player in inflammation and the development of various inflammation-mediated disorders, with nucleotide-binding domain and leucine-rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here an overview about the cellular signaling pathways underlying nuclear factor “kappa-light-chain-enhancer” of activated B-cells (NF-κB)- and NLRP3-mediated inflammatory processes, and the pathogenesis of the inflammatory diseases atherosclerosis and non-alcoholic fatty liver disease (NAFLD) is provided; next, the current state of knowledge for drug-based and dietary-based interventions for treating cardiovascular diseases and NAFLD is discussed. To date, one of the most important antioxidants in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti-inflammatory activity. Recent publications suggest that vitamin E-and possibly metabolites of vitamin E-are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.

Andrew Slivka, Cameron Rink, David Paoletto, Chandan K Sen

FASEB J . 2020 Jul 20. doi: 10.1096/fj.201902216RR. Online ahead of print.

Abstract

The purpose of this study was to characterize the effects of tocotrienol form of vitamin E (TCT) on platelet function in patients with stroke or transient ischemic attack (TIA). A double blind, randomized, single center phase II clinical trial was conducted comparing placebo (PBO) and 400 and 800 mg TCT daily for a year in 150 patients with a sentinel ischemic stroke or TIA event in the prior 6 months. Platelet function was measured at baseline and then, at 3 month intervals for a year, using light transmission aggregometry. The incidence of aspirin resistance in aspirin-treated patients or platelet inhibition in patients on clopidogrel alone was compared between the three treatment groups. Results showed that in patients taking aspirin and clopidogrel, the incidence of aspirin resistance was significantly decreased from 40% in PBO-treated patients to 9% in the 400 mg TCT group and 25% in the TCT 800 mg group (P = .03). In conclusion, patients on aspirin and clopidogrel had a higher incidence of aspirin resistance than all patients treated with aspirin alone and TCT decreased the frequency of aspirin resistance in this group.