Quantification of age-related changes of α-tocopherol in lysosomal membranes in murine tissues and human fibroblasts.
Considering the biological function of α-tocopherol (α-Toc) as a potent protective factor against oxidative stress, this antioxidant is in the focus of aging research. To understand the role of α-Toc during aging we investigated α-Toc concentrations in young and aged primary human fibroblasts after supplementation with RRR-α-Toc. Additionally, α-Toc contents were determined in brain, kidney, and liver tissue of 10 week-, 18 month-, and 24 month-old mice, which were fed a standard diet containing 100 mg/kg dl-α-tocopheryl acetate. α-Toc concentrations in isolated lysosomes and the expression of the α-Toc transport proteins Niemann Pick C1 (NPC1), Niemann Pick C2 (NPC2), and lipoprotein lipase were also analyzed. Obtained data show a significant age-related increase of α-Toc in murine liver, kidney, and brain tissue as well as in human dermal fibroblasts. Also liver and kidney lysosomes are marked by elevated α-Toc contents with aging. NPC1 and NPC2 protein amounts are significantly decreased in adult and aged murine kidney tissue. Also aged human dermal fibroblasts show decreased NPC1 amounts. Supplementation of young and aged fibroblasts led also to decreased NPC1 amounts, suggesting a direct role of this protein in α-Toc distribution. Our results indicate an age-dependent increase of α-Toc in different murine tissues as well as in human fibroblasts. Furthermore saturation and intracellular distribution of α-Toc seem to be strongly dependent on the availability of this vitamin as well as on the presence of the lysosomal protein NPC1. © 2016 BioFactors, 42(3):307-315, 2016.
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
Jeannette
J
König
Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany.
Fabian
F
Besoke
Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany.|Department of Biofunctionality and Safety of Food, Institute of Biological Chemistry and Nutritional Science, University of Hohenheim, Stuttgart, Germany.
Wolfgang
W
Stuetz
Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University Jena, Germany.
Angelika
A
Malarski
Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University Jena, Germany.
Gerhard
G
Jahreis
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Tilman
T
Grune
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Annika
A
Höhn
D000328:Adult; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008071:Lipoprotein Lipase / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D000077296:Niemann-Pick C1 Protein; D018384:Oxidative Stress / Q000187:drug effects; D033921:Vesicular Transport Proteins; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000378:metabolism*
D000975:Antioxidants; D002352:Carrier Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; C104585:NPC2 protein, human; D000077296:Niemann-Pick C1 Protein; D033921:Vesicular Transport Proteins; D008071:Lipoprotein Lipase; D024502:alpha-Tocopherol
aging; lipid peroxidation; lysosomes; oxidative stress; α-tocopherol