Hepatic Adaptation Compensates Inactivation of Intestinal Arginine Biosynthesis in Suckling Mice

Marion, Vincent; Sankaranarayanan, Selvakumari; Theije, Chiel de; Dijk, Paul van; Hakvoort, T. B. M.; Lamers, Wouter H.; Köhler, S. Eleonore

doi:10.1371/journal.pone.0067021

Cited by 8 publications

(12 citation statements)

References 51 publications

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“…Strains were originally obtained from The Jackson Laboratory: C57BL/6J, 000664; B6.129S7-Asl tm1Brle /J, 018830; B6.129P2-Lyz2 tm1(cre)Ifo /J, 004781; C57BL/6J-Tg(Itgax-cre,-EGFP) 4097Ach/J, 007567; B6.Cg-Tg(Tek-cre)1Ywa/J, 008863). Ass1 flox/flox ;Tie2-cre mice were a gift from S. E. Kohler (22). Mice for M. tuberculosis infections were transferred to the Laboratory Animal Medical Services biosafety level 3 facility at the University of Cincinnati 1 wk prior to inoculation.…”

Section: Methodsmentioning

confidence: 99%

“…3D). To exclude a possible role for L-argininosuccinate, the intermediate of L-ARG synthesis from L-CIT, in inhibiting immune function, we crossed Ass1 flox/flox (22) with Tie2-and Lyz2-cre-expressing mice. M. bovis BCG-infected Ass1 flox/flox ;Tie2-cre, and Ass1 flox/flox ; Lyz2 cre/cre mice displayed an increase in mycobacterial load in the lung and spleen as compared with controls ( Supplemental Fig.…”

Section: Myeloid L-arg Synthesis Enhances Host Defense Against Mycobamentioning

confidence: 99%

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l-Arginine Synthesis from l-Citrulline in Myeloid Cells Drives Host Defense against Mycobacteria In Vivo

Lange

McKell

Schmidt

et al. 2019

The Journal of Immunology

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Immunonutrition as a therapeutic approach is rapidly gaining interest in the fight against infection. Targeting l-arginine metabolism is intriguing, considering this amino acid is the substrate for antimicrobial NO production by macrophages. The importance of l-arginine during infection is supported by the finding that inhibiting its synthesis from its precursor l-citrulline blunts host defense. During the first few weeks following pulmonary mycobacterial infection, we found a drastic increase in l-citrulline in the lung, even though serum concentrations were unaltered. This correlated with increased gene expression of the l-citrulline–generating (i.e., iNOS) and l-citrulline–using (i.e., Ass1) enzymes in key myeloid populations. Eliminating l-arginine synthesis from l-citrulline in myeloid cells via conditional deletion of either Ass1 or Asl resulted in increased Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium tuberculosis H37Rv burden in the lungs compared with controls. Our data illustrate the necessity of l-citrulline metabolism for myeloid defense against mycobacterial infection and highlight the potential for host-directed therapy against mycobacterial disease targeting this nutrient and/or its metabolic pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Myeloid L-arg Synthesis Enhances Host Defense Against Mycobamentioning

confidence: 99%

l-Arginine Synthesis from l-Citrulline in Myeloid Cells Drives Host Defense against Mycobacteria In Vivo

Lange

McKell

Schmidt

et al. 2019

The Journal of Immunology

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“…Endothelial Ass- deficient ( Ass fl/fl /Tie2Cre tg/− ) mice were generated by crossing animals carrying the floxed allele Ass fl/fl [23] with Tie2Cre mice. The endothelial knockout animals will be designated as Ass-KO Tie2 , and the Ass fl/fl mice as controls.…”

Section: Methodsmentioning

confidence: 99%

“…The endothelial knockout animals will be designated as Ass-KO Tie2 , and the Ass fl/fl mice as controls. We have previously shown that Ass fl/fl mice are indistinguishable from their wild type littermates [23]. 12- and 34-week-old male and female mice were used for the experiments.…”

Section: Methodsmentioning

confidence: 99%

Endothelial Arginine Resynthesis Contributes to the Maintenance of Vasomotor Function in Male Diabetic Mice

et al. 2014

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AimArgininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice.Methods and ResultsEndothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/− = Ass-KOTie2) were generated by crossing Assfl/fl mice ( = control) with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP) was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively) in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO) were significantly reduced when compared to diabetic control mice.ConclusionsAbsence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes.

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“…Got1은 amino acid metabolism에 중요한 효소로서 aspartate 에서 glutamate에게 α-amino group의 reversible transfer를 촉매한다 [14]. 많이 존재하고 있는 조직으로는 liver, heart, skeletal muscle, kidneys, brain, red blood cells이며 liver…”

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Expressional Analysis of Two Genes (Got1 andMat1) Up-regulated by Starvation Stress

Park¹,

Kwon²,

Lee³

et al. 2014

Journal of Life Science

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Hepatic Adaptation Compensates Inactivation of Intestinal Arginine Biosynthesis in Suckling Mice

Cited by 8 publications

References 51 publications

l-Arginine Synthesis from l-Citrulline in Myeloid Cells Drives Host Defense against Mycobacteria In Vivo

l-Arginine Synthesis from l-Citrulline in Myeloid Cells Drives Host Defense against Mycobacteria In Vivo

Endothelial Arginine Resynthesis Contributes to the Maintenance of Vasomotor Function in Male Diabetic Mice

Expressional Analysis of Two Genes (Got1 andMat1) Up-regulated by Starvation Stress

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