l-arginine uptake, the citrulline–NO cycle and arginase II in the rat brain: an in situ hybridization study

Braissant, Olivier; Gotoh, Tomomi; Loup, Marc; Mori, Masataka; Bachmann, C.

doi:10.1016/s0169-328x(99)00151-5

Cited by 111 publications

(85 citation statements)

References 47 publications

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“…It has been reported that arginase II mRNA is present ubiquitously in nNOS-positive neurons. 21) Therefore, we presume that arginase II regulates nNOS-dependent NO production followed by neurite outgrowth in PC12h cells.…”

Section: Discussionmentioning

confidence: 92%

Expression of Functional Nitric Oxide Synthase for Neuritogenesis in PC12h Cells

Yamazaki

Chiba

2006

JOURNAL OF HEALTH SCIENCE

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We have previously demonstrated that a natural iridoid compound, genipin, induces neurite outgrowth mediated by nitric oxide (NO) production in PC12h cells. However, genipin could not induce neurite outgrowth by PC12 cells, the parental cells of PC12h cells. The difference in neuritogenic response to genipin may be due to a lack of neuronal NO synthase (NOS) protein, most likely neuronal NOS, in PC12 cells. In this study, we have investigated whether neuronal NOS protein innately expressed in PC12h cells plays any functional role in neuritogenesis. LLysine and L-norvaline, inhibitors of arginase which uses the same substrate as NOS, significantly induced neurite outgrowth in PC12h cells but not in PC12 cells. In PC12h cells, L-lysine-induced neurite outgrowth was completely inhibited by a nonselective NOS inhibitor N G -nitro-L-arginine methyl ester (L-NAME) but was not inhibited by its negative isomer D-NAME, suggesting that up-regulation of NOS activity by arginase inhibitors with increasing intracellular concentrations of substrate induces neuritogenesis in NOS-expressing cells. Thus, it is concluded that innately expressed neuronal NOS has a functional role in neuritogenesis in PC12h cells.

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Section: Discussionmentioning

confidence: 92%

Expression of Functional Nitric Oxide Synthase for Neuritogenesis in PC12h Cells

Yamazaki

Chiba

2006

JOURNAL OF HEALTH SCIENCE

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“…32 Centrally, some studies have suggested that NO can enhance reflex bradycardia and depressor response 33,34 ; others believe that increased NO can set BP at a higher level. 35 Given that arginase II may reciprocally regulate NO bioavailability, it is also possible that a lack of arginase II may result in a central resetting of BP.…”

Section: Discussionmentioning

confidence: 99%

Arginase II Knockout Mouse Displays a Hypertensive Phenotype Despite a Decreased Vasoconstrictory Profile

et al. 2009

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Abstract-Arginase upregulation is associated with aging and cardiovascular diseases. In this study we report on the cardiovascular phenotype of the arginase II knockout (KO) mouse. We demonstrate that vascular sensitivity and reactivity altered over time in these animals such that no influence on responses to vasoconstrictor activity was observed in 7-week-old KO mice, but dampened responses to norepinephrine and phenylephrine were observed by 10 and 15 weeks with Rho kinase influencing these effects in the 15-week-old animals. rginase, a key hepatic urea cycle enzyme, hydrolyzes L-arginine to urea and L-ornithine and is responsible for the disposal of excess nitrogen resulting from amino acid and nucleotide metabolism. This enzyme, once thought to be largely confined to the liver, is now known to exist extrahepatically in Ն2 isoforms, arginase I and II. Each isoform is encoded by 2 separate genes, which differ in intracellular and tissue expression, gene transcription, and transduction regulators, as well as metabolism. Arginase I is a cytosolic enzyme abundantly expressed in the liver, 1 whereas mitochondrial arginase II is ubiquitously expressed in extrahepatic tissues, including the vasculature and the kidney. 2 Together with the production of urea, arginase is also responsible for the biosynthesis of polyamines and the amino acids ornithine, proline, and glutamate. Vascular endothelial and smooth muscle cells express both arginase I and II, although the distribution appears vessel and species dependent. 3,4 Importantly, arginase II appears to be the predominant isoenzyme in human endothelial cells. 3,4 Because arginase and NO synthase share L-arginine as their precursor substrate, arginase has been postulated to inhibit NO synthesis by competing with endothelial NO synthase (eNOS) for L-arginine. However, on closer examination, a much higher L-arginine affinity of eNOS (Michaelis constantϭϷ2 to 20 mol/L) than that of arginase (Michaelis constantϭϷ1 to 5 mmol/L) makes this competition kinetically unlikely; however, inducible NO synthase-mediated S-nitrosylation of arginase can decrease the Michaelis constant of arginase to a level where it can compete with eNOS. 5 Furthermore, studies examining arginine metabolism in activated macrophages show that the majority of L-arginine is consumed for the production of urea rather than NO, such that when arginase is inhibited or the culture medium is supplemented with L-arginine, increased NO synthesis is observed. 6 In endothelial cells, inhibition of arginase stimulates NO production, 7 whereas overexpression of arginase I or II decreases intracellular L-arginine concentrations and suppresses NO synthesis. 8 Lastly, it has been shown recently that arginase II is found in the mitochondria where is regulates eNOS. 9 NO is an important vasodilator and antiproliferative and antiatherogenic compound. In various models of hypertension, increased arginase expression or activity is associated with increased vascular proliferation 10 and decreased NO bioavailability, ...

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“…Arginine is supplied to neurones by extraction from the blood through cationic amino acid transporters and by protein breakdown. 19 Arginine is also recycled from citrulline in many tissues, including the brain, and it is this pathway that requires ASL. Arginine is the precursor to many compounds, including nitric oxide and creatine.…”

Section: Discussionmentioning

confidence: 99%

Liver transplantation for argininosuccinic aciduria: Clinical, biochemical, and metabolic outcome

et al. 2007

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We report successful liver transplantation in a young adult with argininosuccinic aciduria but without cirrhosis. Plasma amino acid profile normalized and brain magnetic resonance spectroscopy indicated improved metabolism after transplantation. The general well-being of the patient and his quality of life improved. We suggest that orthotopic liver transplantation should be considered for patients with argininosuccinic aciduria even in the absence of cirrhosis, with the aim of correcting (at least in part) central nervous system metabolism, thereby preventing further neurological deterioration. Liver Transpl 14: 41-45, 2008.

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l-arginine uptake, the citrulline–NO cycle and arginase II in the rat brain: an in situ hybridization study

Cited by 111 publications

References 47 publications

Expression of Functional Nitric Oxide Synthase for Neuritogenesis in PC12h Cells

Expression of Functional Nitric Oxide Synthase for Neuritogenesis in PC12h Cells

Arginase II Knockout Mouse Displays a Hypertensive Phenotype Despite a Decreased Vasoconstrictory Profile

Liver transplantation for argininosuccinic aciduria: Clinical, biochemical, and metabolic outcome

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