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Impaired L-arginine metabolism marks endothelial dysfunction in CD73-deficient mice.

Abstract

Changes in the ecto-5'-nucleotidase activity-an extracellular nucleotide catabolic enzyme may lead to the inflammation and endothelial dysfunction. We investigated the effect of CD73 deletion on the endothelial function and L-arginine metabolism in various age groups of mice. 1-,3-,6-, and 12-month-old, male C57BL/6 J wild type (WT) and C57BL/6 J CD73-/- (CD73-/-) mice were used. Blood samples were used for the analysis of adenine nucleotide concentrations. Serum samples were analyzed for the concentration of amino acids, Interleukin 6 (IL-6), Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and endothelial nitric oxide synthase (eNOS) level. Serum and aortic nitrate/nitrite, as well as aortic arginase and NOS activity in endothelial cells (EC) were evaluated. CD73 deletion led to age-dependent increase in IL-6, ICAM-1, and VCAM-1 concentration compared to WT. All CD73-/- mice age groups were characterized by reduced L-Arginine concentration and eNOS level. Significantly lower NOS activity was noticed in EC isolated from CD73-/- mice lungs in comparison to EC isolated from WT lungs. The L-Arginine/ADMA ratio in the CD73-/- decreased in age-dependent manner in comparison to WT. The nitrate/nitrite ratio was reduced in serum and in aortas of 6-month-old CD73-/- mice as compared to WT. The ornithine/arginine and ornithine/citrulline ratios were increased in CD73-/- compared to controls. Blood (erythrocyte) Adenosine-5'-triphosphate and Adenosine-5'-diphosphate levels were reduced in favor to higher blood Adenosine-5'-monophosphate concentration in CD73-/- mice in comparison to WT. The CD73 deletion leads to the development of age-dependent endothelial dysfunction in mice, associated with impaired L-arginine metabolism. CD73 activity seems to protect endothelium.

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  • Authors+Show Affiliations

    ,

    Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdańsk, Poland.

    ,

    Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdańsk, Poland. Department of Physiology, Medical University of Gdansk, Gdańsk, Poland.

    ,

    Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdańsk, Poland.

    ,

    Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdańsk, Poland.

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    Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdansk, Gdańsk, Poland.

    ,

    Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdańsk, Poland.

    Department of Biochemistry, Medical University of Gdansk, Debinki 1, 80-211, Gdańsk, Poland. eslom@gumed.edu.pl.

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    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31093850

    Citation

    Mierzejewska, P, et al. "Impaired L-arginine Metabolism Marks Endothelial Dysfunction in CD73-deficient Mice." Molecular and Cellular Biochemistry, 2019.
    Mierzejewska P, Zabielska MA, Kutryb-Zajac B, et al. Impaired L-arginine metabolism marks endothelial dysfunction in CD73-deficient mice. Mol Cell Biochem. 2019.
    Mierzejewska, P., Zabielska, M. A., Kutryb-Zajac, B., Tomczyk, M., Koszalka, P., Smolenski, R. T., & Slominska, E. M. (2019). Impaired L-arginine metabolism marks endothelial dysfunction in CD73-deficient mice. Molecular and Cellular Biochemistry, doi:10.1007/s11010-019-03537-4.
    Mierzejewska P, et al. Impaired L-arginine Metabolism Marks Endothelial Dysfunction in CD73-deficient Mice. Mol Cell Biochem. 2019 May 15; PubMed PMID: 31093850.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Impaired L-arginine metabolism marks endothelial dysfunction in CD73-deficient mice. AU - Mierzejewska,P, AU - Zabielska,M A, AU - Kutryb-Zajac,B, AU - Tomczyk,M, AU - Koszalka,P, AU - Smolenski,R T, AU - Slominska,E M, Y1 - 2019/05/15/ PY - 2018/10/17/received PY - 2019/04/12/accepted PY - 2019/5/17/entrez KW - Adenosine KW - Ecto-5′-nucleotidase KW - Endothelial dysfunction KW - Endothelium KW - L-Arginine metabolism KW - Nucleotide metabolism JF - Molecular and cellular biochemistry JO - Mol. Cell. Biochem. N2 - Changes in the ecto-5'-nucleotidase activity-an extracellular nucleotide catabolic enzyme may lead to the inflammation and endothelial dysfunction. We investigated the effect of CD73 deletion on the endothelial function and L-arginine metabolism in various age groups of mice. 1-,3-,6-, and 12-month-old, male C57BL/6 J wild type (WT) and C57BL/6 J CD73-/- (CD73-/-) mice were used. Blood samples were used for the analysis of adenine nucleotide concentrations. Serum samples were analyzed for the concentration of amino acids, Interleukin 6 (IL-6), Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and endothelial nitric oxide synthase (eNOS) level. Serum and aortic nitrate/nitrite, as well as aortic arginase and NOS activity in endothelial cells (EC) were evaluated. CD73 deletion led to age-dependent increase in IL-6, ICAM-1, and VCAM-1 concentration compared to WT. All CD73-/- mice age groups were characterized by reduced L-Arginine concentration and eNOS level. Significantly lower NOS activity was noticed in EC isolated from CD73-/- mice lungs in comparison to EC isolated from WT lungs. The L-Arginine/ADMA ratio in the CD73-/- decreased in age-dependent manner in comparison to WT. The nitrate/nitrite ratio was reduced in serum and in aortas of 6-month-old CD73-/- mice as compared to WT. The ornithine/arginine and ornithine/citrulline ratios were increased in CD73-/- compared to controls. Blood (erythrocyte) Adenosine-5'-triphosphate and Adenosine-5'-diphosphate levels were reduced in favor to higher blood Adenosine-5'-monophosphate concentration in CD73-/- mice in comparison to WT. The CD73 deletion leads to the development of age-dependent endothelial dysfunction in mice, associated with impaired L-arginine metabolism. CD73 activity seems to protect endothelium. SN - 1573-4919 UR - https://www.unboundmedicine.com/medline/citation/31093850/Impaired_L-arginine_metabolism_marks_endothelial_dysfunction_in_CD73-deficient_mice L2 - https://doi.org/10.1007/s11010-019-03537-4 DB - PRIME DP - Unbound Medicine ER -