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Arginase II reduces arginine availability and nitric oxide production during endotoxemia
Author(s) -
Marini Juan C,
Didelija Inka C,
Lee Brendan
Publication year - 2011
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.25.1_supplement.983.20
Subject(s) - arginase , arginine , nitric oxide , intracellular , endocrinology , medicine , chemistry , nitric oxide synthase , biochemistry , biology , amino acid
Arginase is the main pathway for arginine (Arg) disposal and it has been reported that it regulates intracellular Arg availability for nitric oxide (NO) synthesis during endotoxemia. To test the hypothesis that arginase II not only regulates intracellular, but also whole body Arg availability, a multitracer study was conducted in conscious wild type (WT) and arginase II ko (ArgII−/−) mice after a dose of LPS (7 mg/kg). LPS reduced the rate of appearance (Ra) of Arg in WT mice by ~40% (P<0.001), but had no effect in ArgII−/− animals when compared to saline treated mice. Ra phenylalanine was unchanged (P>0.22) indicating that there was no difference in whole body protein degradation among genotypes and treatments. De novo Arg synthesis was reduced (P<0.001) by ~50% in LPS treated WT mice, but was unaffected in ArgII−/− animals. NO production in LPS treated ArgII−/− mice was 2 fold greater than in their WT counterparts (14 vs 7 μmol•kg −1 •h −1 ; P < 0.001). In a follow up study, Ra Arg was clamped in LPS treated WT mice by infusing Arg i.v. to match the Ra Arg of the ArgII−/− mice. Despite similar Ra Arg between the two genotypes, NO production in ArgII−/− mice was 1.6 fold greater than in WT mice (P<0.002). Arginase II reduces NO synthesis by decreasing whole body availability of Arg (reducing Ra arginine and de novo Arg synthesis), as well as by the intracellular mechanisms previously described. Support: USDA 2533771314 and NIH KO1 RR24173.