LRP1 Functions as an Atheroprotective Integrator of TGFβ and PDGF Signals in the Vascular Wall: Implications for Marfan Syndrome

BACKGROUND: The multifunctional receptor LRP1 controls expression, activity and trafficking of the PDGF receptor-β in vascular smooth muscle cells (VSMC). LRP1 is also a receptor for TGFβ1 and is required for TGFβ mediated inhibition of cell proliferation. METHODS AND PRINCIPAL FINDINGS: We show that loss of LRP1 in VSMC (smLRP(−)) in vivo results in a Marfan-like syndrome with nuclear accumulation of phosphorylated Smad2/3, disruption of elastic layers, tortuous aorta, and increased expression of the TGFβ target genes thrombospondin-1 (TSP1) and PDGFRβ in the vascular wall. Treatment of smLRP1(−) animals with the PPARγ agonist rosiglitazone abolished nuclear pSmad accumulation, reversed the Marfan-like phenotype, and markedly reduced smooth muscle proliferation, fibrosis and atherosclerosis independent of plasma cholesterol levels. CONCLUSIONS AND SIGNIFICANCE: Our findings are consistent with an activation of TGFβ signals in the LRP1-deficient vascular wall. LRP1 may function as an integrator of proliferative and anti-proliferative signals that control physiological mechanisms common to the pathogenesis of Marfan syndrome and atherosclerosis, and this is essential for maintaining vascular wall integrity

Fluorescence Detection-FIA for ppb Levels of Bromate with Trifluoperazine

Abstract The fluorescence of tifluoperazine at EX:300 nm and EM:485 nm was changed into non-fluorescent substance in the presence of bromate under acidic conditions, and the fluorescence detection-FIA of trace amounts of the bromate was developed using this phenomenon. In the concentration range of 1-15 μg L -1 , the bromate analysis was able to obtain a good straight line and eighteen samples per hour were measured. For 7.5 μg L -1 of bromate, the relative standard deviation(RSD) was 2.03 %(n=5) and the detection limit (3σ) was 1.47 μg L -1

Radiological impact of TEPCO\u27s Fukushima Dai-ichi Nuclear Power Plant accident on invertebrates in the coastal benthic food web

Radioactive cesium (134Cs and 137Cs) concentrations in invertebrates of benthic food web (10 taxonomic classes with 46 identified families) collected from wide areas off Fukushima Prefecture (3e500 m depth) were inspected from July 2011, four months after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, to August 2013 to elucidate time-series trends among taxa and areas. Cesium-137 was detected in seven classes (77% of 592 specimens). Higher 137Cs concentrations within detected data were often found in areas near or south of the FDNPP, which is consistent with the reported spatial distribution of 137Cs concentrations in highly contaminated seawater and sediments after the FDNPP accident. Overall 137Cs concentrations in invertebrates, the maxima of which (290 Bq kg␣1-wet in the sea urchin Glyp- tocidaris crenularis) were lower than in many demersal fishes, had decreased exponentially with time, and exhibited taxon-specific decreasing trends. Concentrations in Bivalvia and Gastropoda decreased clearly with respective ecological half-lives of 188 d and 102 d. In contrast, decreasing trends in Mala- costraca and Polychaeta were more gradual, with longer respective ecological half-lives of 208 d and 487 d. Echinoidea showed no consistent trend, presumably because of effects of contaminated sediments taken into their digestive tract. Comparison of 137Cs concentrations in the invertebrates and those in seawater and sediments suggest that contaminated sediments are the major source of continuing contamination in benthic invertebrates, especially in Malacostraca and Polychaeta

PGC-1α-Mediated Branched-Chain Amino Acid Metabolism in the Skeletal Muscle

<div><p>Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain α-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.</p></div