Arginase Activities and Global Arginine Bioavailability in Wild-Type and ApoE-Deficient Mice: Responses to High Fat and High Cholesterol Diets

Abstract Increased catabolism of arginine by arginase is increasingly viewed as an important pathophysiological factor in cardiovascular disease, including atherosclerosis induced by high cholesterol diets. Whereas previous studies have focused primarily on effects of high cholesterol diets on arginase expression and arginine metabolism in specific blood vessels, there is no information regarding the impact of lipid diets on arginase activity or arginine bioavailability at a systemic level. We, therefore, evaluated the effects of high fat (HF) and high fat-high cholesterol (HC) diets on arginase activity in plasma and tissues and on global arginine bioavailability (defined as the ratio of plasma arginine to ornithine + citrulline) in apoE 2/2 and wild-type C57BL/6J mice. HC and HF diets led to reduced global arginine bioavailability in both strains. The HC diet resulted in significantly elevated plasma arginase in both strains, but the HF diet increased plasma arginase only in apoE 2/2 mice. Elevated plasma arginase activity correlated closely with increased alanine aminotransferase levels, indicating that liver damage was primarily responsible for elevated plasma arginase. The HC diet, which promotes atherogenesis, also resulted in increased arginase activity and expression of the type II isozyme of arginase in multiple tissues of apoE 2/2 mice only. These results raise the possibility that systemic changes in arginase activity and global arginine bioavailability may be contributing factors in the initiation and/or progression of cardiovascular disease

Pulmonary toxicity and lung tumorigenic potential of surrogate metal oxides in gas metal arc welding–stainless steel fume: Iron as a primary mediator versus chromium and nickel

In 2017, the International Agency for Research on Cancer classified welding fumes as “car- cinogenic to humans” (Group 1). Both mild steel (MS) welding, where fumes lack carcino- genic chromium and nickel, and stainless steel (SS) increase lung cancer risk in welders; therefore, further research to better understand the toxicity of the individual metals is needed. The objectives were to (1) compare the pulmonary toxicity of chromium (as Cr(III) oxide [Cr2O3] and Cr (VI) calcium chromate [CaCrO4]), nickel [II] oxide (NiO), iron [III] oxide (Fe2O3), and gas metal arc welding-SS (GMAW-SS) fume; and (2) determine if these metal oxides can promote lung tumors. Lung tumor susceptible A/J mice (male, 4–5 weeks old) were exposed by oropharyngeal aspiration to vehicle, GMAW-SS fume (1.7 mg), or a low or high dose of surrogate metal oxides based on the respective weight percent of each metal in the fume: Cr2O3 + CaCrO4 (366 + 5 μg and 731 + 11 μg), NiO (141 and 281 μg), or Fe2O3 (1 and 2 mg). Bronchoalveolar lavage, histopathology, and lung/liver qPCR were done at 1, 7, 28, and 84 days post-aspiration. In a two-stage lung carcinogenesis model, mice were initi- ated with 3-methylcholanthrene (10 μg/g; intraperitoneal; 1x) or corn oil then exposed to metal oxides or vehicle (1 x/week for 5 weeks) by oropharyngeal aspiration. Lung tumors were counted at 30 weeks post-initiation. Results indicate the inflammatory potential of the metal oxides was Fe2O3 \u3e Cr2O3 + CaCrO4 \u3e NiO. Overall, the pneumotoxic effects were negligible for NiO, acute but not persistent for Cr2O3 + CaCrO4, and persistent for the Fe2O3 exposures. Fe2O3, but not Cr2O3 + CaCrO4 or NiO significantly promoted lung tumors. These results provide experimental evidence that Fe2O3 is an important mediator of welding fume toxicity and support epidemiological findings and the IARC classification

Arginase activities and global arginine bioavailability in wild-type and ApoE-deficient mice: Responses to high fat and high cholesterol diets

Increased catabolism of arginine by arginase is increasingly viewed as an important pathophysiological factor in cardiovascular disease, including atherosclerosis induced by high cholesterol diets. Whereas previous studies have focused primarily on effects of high cholesterol diets on arginase expression and arginine metabolism in specific blood vessels, there is no information regarding the impact of lipid diets on arginase activity or arginine bioavailability at a systemic level. We, therefore, evaluated the effects of high fat (HF) and high fat-high cholesterol (HC) diets on arginase activity in plasma and tissues and on global arginine bioavailability (defined as the ratio of plasma arginine to ornithine + citrulline) in apoE-/- and wild-type C57BL/6J mice. HC and HF diets led to reduced global arginine bioavailability in both strains. The HC diet resulted in significantly elevated plasma arginase in both strains, but the HF diet increased plasma arginase only in apoE-/- mice. Elevated plasma arginase activity correlated closely with increased alanine aminotransferase levels, indicating that liver damage was primarily responsible for elevated plasma arginase. The HC diet, which promotes atherogenesis, also resulted in increased arginase activity and expression of the type II isozyme of arginase in multiple tissues of apoE-/- mice only. These results raise the possibility that systemic changes in arginase activity and global arginine bioavailability may be contributing factors in the initiation and/or progression of cardiovascular disease

Performance practice and analysis of Johann Sebastian Bach's Aria for tenor and flute obbligato, Wo wird in diesem Jammertale, from Cantata BWV 114

This creative project explores the musical performer’s obligation to fully investigating traditional baroque performance practices, and how such study applies to Johann Sebastian Bach’s Wo wird in diesem Jammertale, a sacred aria for tenor, flute obbligato, and continuo from his Cantata BWV 114. This document researches major treatises on baroque performance practice, including Johann Joachim Quantz’s respected On Playing the Flute, to provide a thorough performance practice analysis of this aria. Furthermore, the author completes a formal theoretical analysis of the aria in order to further explore performance possibilities involving the relationship between text and harmonic structure. This project especially highlights specific ways to achieve both an educated preparation and more musically accurate performance of historical music using modern instruments.School of MusicThesis (M.M.

Performance practice and analysis of Johann Sebastian Bach's Aria for tenor and flute obbligato, Wo wird in diesem Jammertale, from Cantata BWV 114

This creative project explores the musical performer’s obligation to fully investigating traditional baroque performance practices, and how such study applies to Johann Sebastian Bach’s Wo wird in diesem Jammertale, a sacred aria for tenor, flute obbligato, and continuo from his Cantata BWV 114. This document researches major treatises on baroque performance practice, including Johann Joachim Quantz’s respected On Playing the Flute, to provide a thorough performance practice analysis of this aria. Furthermore, the author completes a formal theoretical analysis of the aria in order to further explore performance possibilities involving the relationship between text and harmonic structure. This project especially highlights specific ways to achieve both an educated preparation and more musically accurate performance of historical music using modern instruments.Thesis (M.M.)School of Musi

Induction of arginase mRNA and protein in apoE^−/− mice on HC diet.

<p>(A) Effect of HC diet on arginase I and II mRNAs in heart, lung, spleen and kidney. mRNA levels are expressed relative to the levels in apoE^−/− mice on standard diet (arbitrarily set to 1.0 for each tissue and indicated by dotted line). Values are means ± SE for n = 5–7 in each group. *p<0.05 vs standard diet. (B) Effect of HC diet on arginase II protein abundance in lung, spleen and kidney. For each tissue, the upper panel represents arginase II and the lower panel GAPDH. Western blots of extracts from tissues of 5 representative animals on each diet are shown. Amounts of protein loaded in each lane were 10 µg (lung and kidney) or 25 µg (spleen). An extract of C57BL/6J whole kidney (20 µg for lung and kidney blots, 3 µg for spleen blot) was used in the first lane of each blot as positive control (+CT) for arginase II. Twenty µg protein from kidney of the arginase II knockout mouse <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015253#pone.0015253-Shi1" target="_blank">[47]</a> was included in the second lane of the kidney blot in order to establish identity of the lowest band as arginase II. (C) Effect of HC diet on arginase I protein abundance in spleen. The upper panel represents arginase I and the lower panel GAPDH. The Western blot represents extracts from spleen (50 µg each lane) of 5 representative animals on each diet and 100 ng of C57BL/6J liver extract (+CT) as positive control. (D) Densitometry of Western blots, represented in arbitrary units (Arginase/GAPDH), was analyzed by Image Quant 5.2 Software. *p<0.01 vs standard diet. Molecular weights are indicated by the following symbols: solid triangles, 39 kDa; solid diamonds, 37 kDa; open triangles, 37 kDa.</p