Localization and differential expression of arginase II in the kidney of male and female mice

Levillain, Olivier; Balvay, Sandra; Peyrol, S

doi:10.1007/s00424-004-1336-8

Cited by 38 publications

(57 citation statements)

References 43 publications

(83 reference statements)

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“…Thus, Arg inhibition exerts its effect by a NOSdependent mechanism. Also, consistent with our observations, incubation of cardiac myocytes with Nor-NOHA (a pharmacologically distinct specific Arg inhibitor) also caused a dose-dependent increase in basal myocardial contractility (logEC 50 , Ϫ5.8 Ϯ 0.8; E max , 1.98 Ϯ 0.23) (Fig. 4B).…”

Section: Resultssupporting

confidence: 90%

“…Given our observation that Arg II appears to be associated with NOS1, and that NOS1-derived NO accentuates myocardial contractility, we hypothesized that inhibition of Arg would increase basal contractility. Consistent with our hypothesis, BEC increased myocardial contractility in a dose-dependent manner [logEC 50 , Ϫ5.8 Ϯ 0.9; E max , 1.8 Ϯ 0.3 (fold increase)] (Fig. 4A).…”

Section: Resultssupporting

confidence: 89%

“…Although myocyte subcellular fractionation and immunoblotting suggested that Arg II is predominantly found in the mitochondria, immunoelectron microscopy conclusively demonstrated that Arg II is confined almost exclusively to the mitochondria. This observation is in agreement with the findings of others who demonstrate Arg II confined to the mitochondria in other cell types (49,50) and is consistent with the putative N-terminal mitochondrial-targeting presequence found in the gene for Arg II (25,26). However, coimmunoprecipitation experiments and WB demonstrated that Arg II is also found in crude SR preparations and immunoprecipitates of NOS1 (known to be found in the SR).…”

Section: Discussionsupporting

confidence: 93%

“…4B). The EC 50 values for BEC and Nor-NOHA are consistent with the K i values of the inhibitors for Arg as described in ref. 27.…”

Section: Resultssupporting

confidence: 86%

“…All data are presented as mean Ϯ SEM, with N indicated for each experimental protocol. For dose-responses, data were fitted by using the software program PRISM 4 (Graphpad, San Diego), and E max and EC 50 were calculated. Statistical analysis was performed by using one-way ANOVA with posttest or unpaired Student's t test, as appropriate.…”

Section: Measurement Of Contractility In Isolated Rat and Mouse Myocymentioning

confidence: 99%

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Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism

Steppan

Ryoo

Schuleri

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Cardiac myocytes contain two constitutive NO synthase (NOS) isoforms with distinct spatial locations, which allows for isoformspecific regulation. One regulatory mechanism for NOS is substrate (L-arginine) bioavailability. We tested the hypothesis that arginase (Arg), which metabolizes L-arginine, constrains NOS activity in the cardiac myocyte in an isoform-specific manner. Arg activity was detected in both rat heart homogenates and isolated myocytes. Although both Arg I and II mRNA and protein were present in whole heart, Arg II alone was found in isolated myocytes. Arg inhibition with S-(2-boronoethyl)-L-cysteine (BEC) augmented Ca 2؉ -dependent NOS activity and NO production in myocytes, which did not depend on extracellular L-arginine. Arg II coimmunoprecipited with NOS1 but not NOS3. Isolation of myocyte mitochondrial fractions in combination with immuno-electron microscopy demonstrates that Arg II is confined primarily to the mitochondria. Because NOS1 positively modulates myocardial contractility, we determined whether Arg inhibition would increase basal myocardial contractility. Consistent with our hypothesis, Arg inhibition increased basal contractility in isolated myocytes by a NOS-dependent mechanism. Both the Arg inhibitors N-hydroxynor-L-arginine and BEC dose-dependently increased basal contractility in rat myocytes, which was inhibited by both nonspecific and NOS1-specific NOS inhibitors N G -nitro-L-arginine methyl ester and S-methyl-L-thiocitrulline, respectively. Also, BEC increased contractility in isolated myocytes from WT and NOS3 but not NOS1 knockout mice. We conclude that mitochondrial Arg II negatively regulates NOS1 activity, most likely by limiting substrate availability in its microdomain. These findings have implications for therapy in pathophysiologic states such as aging and heart failure in which myocardial NO signaling is disrupted. mitochondria ͉ L-arginine pools ͉ spatial confinement

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 89%

Section: Discussionsupporting

confidence: 93%

“…4B). The EC 50 values for BEC and Nor-NOHA are consistent with the K i values of the inhibitors for Arg as described in ref. 27.…”

Section: Resultssupporting

confidence: 86%

Section: Measurement Of Contractility In Isolated Rat and Mouse Myocymentioning

confidence: 99%

See 3 more Smart Citations

Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism

Steppan

Ryoo

Schuleri

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Arginase Inhibitors: A Rational Approach Over One Century

Pudlo

Demougeot

Girard

2016

Medicinal Research Reviews

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Arginase (EC 3.5.3.1) is the bimanganese enzyme that converts L-arginine into ornithine and urea. This enzyme was discovered more than a century ago and early α-amino acids were identified as weak inhibitors. It was only during the 90s, after nitric oxide (NO) was reported as one of the most important biological mediators and when tight interrelation of arginase and NO synthase was found, that the development of arginase inhibitors was accelerated. The regulation of arginase activity by the N-hydroxy-L-arginine (3, NOHA) intermediate of the NO synthesis was the starting point of the N-hydroxy-nor-arginine (21, nor-NOHA) that proved to be the first micromolar inhibitor. The previously known manganese and arginase binding by borate inspired the 2(S)-amino-6-boronohexanoic acid (39, ABH) and S-(2-boronoethyl)-L-cysteine (40, BEC) now both considered as reference compounds in arginase inhibition. The high-resolution crystal structure of arginase and molecular modeling has rendered possible the recent design of (53) the strongest α,α-disubstituted derivatives of ABH. Simultaneously, traditional medicinal plants have contributed as a source of molecular diversity to the discovery of arginase inhibitors. This rational, step-by-step approach serves as guide in the present review where emphasis is placed on structure activity relationships. Highlights exhaustive review on arginase inhibitors highlight is made on rational approach to conception and structure activity relationships evaluation model is systematically mentioned with results.

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Direct production of l-ornithine from casein by commercial digestive enzymes and in situ activated arginase

Gotoh

Kikuchi

Kagaya³

et al. 2010

Bioprocess Biosyst Eng

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There is a great demand for L-ornithine, which is used as a dietary supplement, and in the pharmaceutical industry. In the present study, when milk casein was hydrolyzed at 37 degrees C by using commercial digestive enzymes, namely, Pancreatin F and Protease A, a significant accumulation of L-ornithine in the hydrolysate and the simultaneous disappearance of L-arginine was noted. In a radiometric assay, transient but distinct arginase activity, which was sufficiently high for L-ornithine production, was detected in the hydrolysate for a certain period during casein hydrolysis. On the basis of the results of the enzymatic analyses, arginase was thought to be proteolytically generated from an inactive precursor, which may generally be contained in Pancreatin F, and ultimately degraded by further proteolysis. This conversion process using the above-mentioned digestive enzymes is useful for the production of L-ornithine directly from protein sources that are abundant in nature.

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Localization and differential expression of arginase II in the kidney of male and female mice

Cited by 38 publications

References 43 publications

Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism

Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism

Arginase Inhibitors: A Rational Approach Over One Century

Direct production of l-ornithine from casein by commercial digestive enzymes and in situ activated arginase

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