effect of aging and dietary salt and potassium intake on endothelial pten (phosphatase and tensin homolog on chromosome 10) function衰老和膳食盐和钾的摄入量对内皮pten(磷酸酶和tensin同族体染色体上10)功能.pdfVIP

Effect of Aging and Dietary Salt and Potassium Intake on Endothelial PTEN (Phosphatase and Tensin Homolog on Chromosome 10) Function 1 1 1,2 Wei-Zhong Ying , Kristal J. Aaron , Paul W. Sanders * 1 Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, Center for Free Radical Biology, Center for Aging, and Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Department of Veterans Affairs Medical Center, Birmingham, Alabama, United States of America Abstract Aging promotes endothelial dysfunction, defined as a reduction in bioavailable nitric oxide (NO) produced by the endothelial isoform of nitric oxide synthase (NOS3). This enzyme is critically regulated by phosphorylation by protein kinase B (Akt), which in turn is regulated by the lipid phosphatase, PTEN. The present series of studies demonstrated a reduction in bioavailable NO as the age of rats increased from 1 to 12 months. At 12 months of age, rats no longer demonstrated increases in phosphorylated NOS3 in response to high dietary salt intake. Endothelial cell levels of PTEN increased with age and became refractory to change with increased salt intake. In contrast to the reduction in NO production, endothelial cell production of transforming growth factor-ß (TGF-ß) relative to NO increased progressively with age. In macrovascular endothelial cells, PTEN was regulated in a dose-dependent fashion by TGF-ß, which was further regulated by extracellular [KCl]. When combined with prior studies, the present series of experiments suggested an integral role for PTEN in endothelial cell pathobiolog