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Increased Oxidative Stress and Vascular Aging by Zinc Deficiency in Mice
Author(s) -
Salazar Gloria,
Zhao Yitong,
Feresin Rafaela
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.761.4
Subject(s) - oxidative stress , senescence , nox1 , reactive oxygen species , nox4 , zinc deficiency (plant disorder) , endocrinology , zinc , nadph oxidase , medicine , angiotensin ii , biology , chemistry , microbiology and biotechnology , organic chemistry , blood pressure
Zinc is an essential micronutrient largely recognized by its structural role in enzymes and transcription factors and more recently in signal transduction. Dietary zinc promotes beneficial effects and its deficiency is associated with diverse diseases including cardiovascular and neurodegenerative diseases by incompletely understood mechanisms. Using ApoE KO mice fed zinc deficient (3 ppm zinc), zinc adequate (80 ppm zinc) and zinc supplemented (300 ppm zinc) diets, we found that zinc deficiency accelerates senescence, a hallmark of mammalian aging, which is associated with the onset and progression of cardiovascular disease. In contrast, zinc supplementation ameliorates the increase in senescence induced by Angiotensin II (Ang II), a strong stimulator of vascular aging and disease. Ang II as well as zinc deficiency decreased the expression of the zinc transporters ZnT3, which work to reduce cytosolic zinc levels. Using aortic vascular smooth muscle cells (VSMCs) in vitro , we found that ZnT3 downregulation increases senescence and reactive oxygen species (ROS). In contrast, ZnT3 overexpression prevents Ang II‐induced senescence and reduces ROS levels. Increased ROS production by NADPH oxidase Nox1 is associated with senescence and atherosclerosis. We found that ZnT3 interacts with Nox1 and reduces Nox1‐dependent ROS production. These data suggest that zinc homeostasis dysfunction by decreased expression of ZnT3 promotes senescence and may accelerate atherosclerosis development. The novel regulatory role of ZnT3 on Nox1 function, suggest that dietary zinc interventions may have a broader impact in oxidative stress‐mediated diseases, including cardiovascular and neurodegenerative diseases