Mitochondrial Expression of Arginase II in Male and Female Rat Inner Medullary Collecting Ducts
Laboratoire de Physiopathologie Métabolique et Rénale, Institut National de la Santé et de la Recherche Médicale (INSERM) (OL) and Centre Commun d'Imagerie Laennec (CeCIL) (SB,SP), Université Claude Bernard, Faculté de Médecine Lyon R.T.H. Laennec, Lyon, France
Correspondence to: Dr. Olivier Levillain, Université Claude Bernard, Faculté de Médecine Lyon R.T.H. Laennec, Laboratoire de Physiopathologie Métabolique et Rénale, INSERM U 499, 7, rue G. Paradin, 69372 Lyon Cedex 08, France. E-mail: Olivier.Levillain{at}laennec.univ-lyon1.fr
![]() |
Summary |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key Words: renal zones Western blot cytosol mitochondria electron microscopy
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Arginase II gene is expressed in kidneys of various mammalian species. Significant amounts of arginase II mRNA and protein were detected in whole human (Morris et al. 1997), rat, and mouse (Gotoh et al. 1996
; Iyer et al. 1998
; Shi et al. 1998
; Ozaki et al. 1999
; Levillain et al. 2005
) kidneys, whereas arginase II activity was measured in rat (Skrzypek-Osiecka et al. 1983
) and mouse (Kochakian and Stettner 1948
; Bradley 1973
; Manteuffel-Cymborowska et al. 1995
) kidneys. In almost all the species studied including rodents, carnivores, omnivores, and lagomorphs, the renal localization of arginase II exhibits similarity and differences (Robinson and Schmidt-Nielsen 1963
; Levillain and Hus-Citharel 1996
; Levillain et al. 2005
). The precise localization of arginase II in the mammalian kidney has been achieved by different experimental approaches. Several years ago we indirectly localized arginase II activity by measuring the production of 14C-urea from viable microdissected tubules incubated in the presence of L-[guanidino-14C]arginine (Levillain et al. 1989
). Whatever the mammalian species considered, the highest levels of urea were constantly produced by the whole proximal straight tubule (PST), suggesting a high expression of arginase II gene in the cortical and medullary PST (CPST and OSPST, respectively) (Levillain and Hus-Citharel 1996
). In addition, depending on the species studied, arginase II gene was expressed in other nephron segments including the proximal convoluted tubules, the medullary thick ascending limbs, and the different portions of the collecting ducts (Levillain and Hus-Citharel 1996
). In kidneys of the male Sprague Dawley rat, a very high level of L-arginine was hydrolyzed by arginase II in CPST, OSPST, and the inner medullary collecting ducts (IMCD) (Levillain et al. 1989
). Recently, another group localized the mature arginase II by immunohistochemistry in the male Wistar rat kidney and observed a strong labeling in CPST and OSPST but not in the different segments of the collecting ducts (Miyanaka et al. 1998
). Inasmuch as the two complementary approaches used to localize arginase II in the rat nephron are not in good agreement, we decided to reevaluate whether the production of urea by IMCD results from an arginase II activity or originates from another metabolic pathway involving the presence of two enzymes. The first enzyme, named arginine decarboxylase, decarboxylates L-arginine to produce agmatine (Morrissey et al. 1995
; Lortie et al. 1996
), and the second enzyme named agmatinase (EC: 3.5.3.11) hydrolyzes agmatine into putrescine and urea (Dallmann et al. 2004
). It is noteworthy that the human agmatinase gene encodes a 352-residue protein with an N-terminal mitochondrial-targeting sequence (Dallmann et al. 2004
).
Transcription of arginase II mRNA leads to a single polypeptide of 354 amino acid residues including a putative NH2-terminal presequence for mitochondrial import (Shi et al. 1998). This arginase II precursor has a molecular weight of
40 kDa, whereas the mature form of arginase II, which is localized within the mitochondria, exhibited a molecular weight of
38 kDa (Gotoh et al. 1996
; Levillain et al. 2005
). The mitochondrial localization of arginase II in the murine OSPST has recently been demonstrated by using a specific and purified antibody raised against arginase II (Levillain et al. 2005
). Interestingly, the relative abundance of mitochondria in the rat PST is clearly several times higher than in IMCD (Pfaller 1982
). Regarding the high rate of L-arginine hydrolyzed by rat IMCD and the low abundance of mitochondria in this nephron segment, one may propose that either arginase II protein is dramatically more concentrated in mitochondria of IMCD compared with those of OSPST or, alternatively, arginase II protein is localized in another subcellular compartment (e.g., cytosol).
The present paper was designed to determine whether the male and female rat IMCD express the arginase II gene and to identify the subcellular localization of the mature arginase II in this nephron segment. To achieve these goals, we developed a specific antibody raised against arginase II that differs from the antibody used by Miyanaka et al. (1998). Soluble proteins were extracted from the main renal zones dissected from the male and female rat kidneys and were analyzed on immunoblots to detect arginase II. Immunofluorescence and immunoelectron microscopy were performed to localize arginase II at the tubular and subcellular levels in dissected inner medulla (IM). In addition, to estimate the relative abundance of arginase II in the cytosol and mitochondria, the soluble proteins of each subcellular compartment were extracted from dissected outer stripe of the outer medulla (osOM) and IM, and analyzed on immunoblots. This experiment also allowed verification of the molecular weight of arginase II in each subcellular compartment.
Our results clearly show that in the male and female rat kidneys our antibody against arginase II allowed the detection on immunoblots of a single peptide of 38 kDa that corresponds to the expected molecular weight of arginase II. The level of arginase II was extremely abundant in all cells of the male and female IMCD and was almost exclusively localized in their mitochondria.
![]() |
Materials and Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Arginase II Antibody
A peptide-derived polyclonal antibody raised against arginase II was prepared by CovalAb (Lyon, France) and used for immunoblotting, immunohistochemistry, and immunoelectron microscopy. To obtain this polyclonal antibody, the conserved amino acid sequence (IASSFGQTREGGHIEC) of the human (Swiss-Prot P78540), mouse (Swiss-Prot O08691), and rat (Swiss-Prot O08701) arginase II was used to produce a synthetic peptide that differs from that of Miyanaka et al. (1998). The synthetic peptide was analyzed by HPLC and conjugated to keyhole limpet hemocyanin via covalent linkage to cysteine. One female New Zealand rabbit was immunized three times with the conjugate using a complete Freund's adjuvant. Arginase II antibody titer was determined by ELISA and immunopurified using a column on which the synthetic peptide was immobilized.
Dissection of the Main Renal Zones
The right and left kidneys of male and female rats were rapidly removed, decapsulated, and cut along the cortico-papillary axis to dissect the six main renal zones [superficial cortex (Cs), deep cortex (Cd), outer stripe of the outer medulla (osOM), inner stripe of the outer medulla (isOM), inner medulla (IM), and papilla (Pap)] at 4C under a stereomicroscope. The dissected tissue was immediately placed in a sterilized Eppendorf tube, frozen, and conserved in liquid nitrogen.
Protein Extraction and Western Blot Analyses
Each frozen renal zone was mixed at 4C with a Turrax homogenizer in the proportion of 100 mg frozen tissue per 2 ml of lysing buffer (Laemmli 1970) containing 1 mM of protease inhibitor cocktail, 1 mM phenylmethylsulfonyl fluoride, and 1 mM benzamidine. The homogenate was centrifuged at 10,000 x g for 30 min at 4C. The concentration of the soluble proteins was determined using the Bradford protein assay (Bradford 1976
).
Fifty µg of soluble proteins from each renal zone were subjected to 10% SDS-PAGE and then transferred to a polyvinylidene difluoride membrane (0.45 µm; Immobilon-P, Millipore, St. Quentin en Yvelines, France) as previously described (Levillain et al. 2005). Proteins were visualized on the membrane with Ponceau S solution to control protein loading and transfer. Membranes were washed twice in TBST (20 mM Tris, pH 7.6, 137 mM NaCl, 0.1% Tween 20) and immersed twice in a blocking solution consisting of 5% fat-free milk powder in TBST for 30 min. Membranes were incubated separately with the three following rabbit polyclonal antibodies raised against arginase II (see above, dilution 1:1,000), the rat-aldose reductase (AR; dilution 1:3,000), and the rat cysteine sulfinate decarboxylase (CSD; dilution 1:1,000) diluted in 5% fat-free milk-TBST. Immunoblots were washed three times for 10 min in TBST and incubated for 60 min with a goat anti-rabbit IgG peroxidase-conjugated diluted 1:10,000 in 5% fat-free milkTBST. Immunoblots were washed three times for 10 min in TBST, and antibody binding was revealed using chemiluminescence (ECL) Western Blotting Kit. ECL detection was performed using Kodak X-MAT film. Low-exposure film was scanned, and the intensity optical densitometry (IOD) of the bands was estimated using the ImagerMaster Total Lab v2.01 program (Pharmacia; Orsay, France).
Subcellular Fractionation for Immunoblot Analyses
The kidneys of four female rats were dissected at 4C under a stereomicroscope to collect their osOM and IM. The dissected tissue was rapidly immersed in a buffer (250 mM sucrose, 10 mM Tris-HCl, pH 7.6, and 1 mM Na2 EDTA) prealably maintained at 4C. The tissue was homogenized using a Potter-Elvehjem glass homogenizer PTFE pestle (Bellco Glass Inc.; Vineland, NJ) and centrifuged at 600 x g for 10 min to remove cell debris and the nuclear fraction. The pellet (P1) was discarded whereas the supernatant (S1) was centrifuged at 9000 x g for 10 min. The pellet (P2) that contained mitochondria was resuspended once in the same buffer and centrifuged again at 9000 x g for 10 min. The supernatant (S2) was centrifuged at 128,000 x g for 45 min (Optima TLA 100.2 Ultracentrifuge; Beckman) to obtain proteins of the cytosolic fraction in the third supernatant. Protein concentrations were determined using the Bradford protein assay (Bradford 1976).
Forty-µg proteins from the cytosolic and mitochondrial fractions were subjected to 10% SDS-PAGE and transferred for Western blot analyses as described above. Membranes were incubated with the rabbit polyclonal antibodies raised against the -subunit F1-ATP synthase (dilution 1:5000) (Moradi-Ameli and Godinot 1983
), core 2 (mitochondrial complex III core protein 2, dilution 1:20,000) (Legros et al. 2001
), arginase II (see above), and the mouse monoclonal antibody raised against the iron sulfur protein (ISP, dilution 1:80,000) (Legros et al. 2001
) diluted in 5% fat-free milkTBST. For the next steps, immunoblots were incubated with a goat anti-rabbit IgG and a goat anti-mouse IgG peroxidase-conjugated diluted each 1:10,000 in 5% fat-free milkTBST and treated as described above.
Indirect Immunofluorescence
Kidneys were rapidly removed, cut along the cortico-papillary axis, dipped in Bouin fixative, and embedded in paraffin. Tissue sections of 47 µm were collected on glass slides (ChemMate; DAKO, Trappes, France), deparaffinized three times in methylcyclohexane (toluene substitute) for 5 min at room temperature (RT), step-rehydrated in 100% ethanol for 5 min, twice in 95% ethanol for 5 min, rinsed in distilled water, and then in phosphate-buffered saline (PBS: 100 mM phosphate buffer, 150 mM NaCl, pH 7.4). Nonspecific sites were coated with PBS supplemented with 0.3% Triton X-100 and 1% BSA (PBST-BSA) for 120 min at RT and incubated overnight at 4C with our purified rabbit polyclonal antibody raised against arginase II (dilution 1:100) in PBST. The slides were rinsed three times in PBST for 5 min and incubated for 120 min at RT with goat anti-rabbit IgG Alexa Fluor 546-conjugated (dilution 1:1,000) (Interchim; Montluçon, France). Slides were washed twice for 510 min in PBST, one time in PBS for 510 min, and incubated with 4',6-diamidine-2-phenylindole dihydrochloride (DAPI, 0.1 µg/ml) in PBS for 30 min at RT. Slides were washed three times in PBS and mounted with Fluoprep (bioMérieux; Marcy l'Etoile, France). Tissue sections were examined with a fluorescent microscope.
Immunoelectron Microscopy
Dissection of IM from male and female rat kidney was performed at 4C. The IM was cut into small pieces (<1 mm3) and fixed for 60 min at 4C in PLP composed of 10 mM metaperiodate, 75 mM lysine, and 2% paraformaldehyde in 37 mM Sorensen's phosphate buffer complemented with 0.2% glutaraldehyde. Pieces of tissues were washed three times in 50 mM Sorensen's phosphate buffer, 200 mM sucrose, and 100 mM lysine monochlorhydrate for 20 min at 4C, dehydrated through a series of washes with 30, 50, 70, and 95% ethanol maintained prealably at 4C for 5 min, and infiltrated with London Resin White (LRWhite; Euromedex, Mundolsheim, France) using 1:1 LRWhite and 4C absolute ethanol for 60 min followed by pure LRWhite at 4C for three periods of 60 min and, finally, embedded in pure LRWhite in gelatin capsules for polymerization at 50C for 48 hr.
Ultrathin sections (80-nm thick) were cut on a RMC MTX ultramicrotome (Elexience; Verrières-le-Buisson, France), mounted on 200-mesh nickel grids coated with polylysine (dilution 1:1,000), and stabilized for 1 day at RT. Immunogold labeling was performed by flotation of grids on drops of reactive media. Nonspecific sites were coated with 1% BSA and 1% normal goat serum in 50 mM Tris-HCl, pH 7.4 for 60 min at RT. Thereafter, incubation was carried out overnight at 4C in a wet chamber with our purified rabbit polyclonal antibody raised against arginase II (dilution 1:100 or 1:150) in 1% BSA, 50 mM Tris-HCl, pH 7.4. Tissue sections were successively washed three times in 50 mM Tris-HCl, pH 7.4 and pH 8.2 at RT, incubated in a wet chamber for 45 min at RT in 1% BSA, 50 mM Tris-HCl, pH 8.2 for 20 min at RT, labeled with a goat anti-rabbit IgG gold-conjugated (20 nm; tebu-bio SA; Le Perray en Yvelines, France) diluted 1:25 in 1% BSA 50 mM Tris-HCl pH 8.2, successively washed three times in 50 mM Tris-HCl pH 8.2 and pH 7.4, and three times in filtrated distilled water. Sections were contrasted with aqueous saturated 3% uranyl acetate for 45 min in darkness and lead citrate for 5 min and observed on a transmission electron microscope (Jeol 1200EX; Tokyo, Japan) equiped with a MegaViewII digital camera and AnalySIS software (Eloise; Roissy Charles de Gaulle, France).
Chemicals
Salts and most chemicals, phenylmethylsulfonylfluoride, benzamidine, Ponceau S solution, secondary anti-IgG antibodies, and Kodak X-MAT films were purchased from Sigma (St. Quentin Fallavier, France). Protease inhibitor cocktail (DAPI) was purchased from Boehringer Mannhein (Strasbourg, France). ECL Western Blotting Kits and ImagerMaster Total Lab v2.01 program were purchased from Amersham (Buckinghamshire, UK and Orsay, France).
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The rat arginase II gene encodes for a protein with a predicted molecular weight of 38,645 Da (Iyer et al. 1998). As expected, our antibody raised against arginase II revealed a band of
38 kDa by Western blotting. This single peptide of arginase II was detected in all renal zones of both female and male rats, but its relative abundance was higher in IM than in the other renal zones. This typical distribution pattern of arginase II characterizes the rat kidney and deeply differs from that of the other mammals that express a very low arginase II activity in their collecting duct (Levillain and Hus-Citharel 1996
). It remains still unexplained for which physiological interests rats expressed arginase II in the collecting duct. The present immunohistological study reveals that within IM, arginase II is highly expressed in IMCD compared to thin descending and ascending limbs of Henle's loop. The level of arginase II is in good agreement with the production of urea in IMCD (Levillain et al. 1989
). Recently, the 38-kDa arginase II was also identified by Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry in isolated IMCD (van Balkom et al. 2004
). Interestingly, IMCD are composed of 90% principal and 10% intercalated cells that differ in morphology and cell functions (Tisher and Madsen 2000
). Intercalated cells are present only in the upper third, but not in the two lower thirds, of the rat inner medulla. Because immunofluorescence of arginase II was homogeneously detected along IMCD, our results clearly indicate that the principal cells express the arginase II gene and suggest that intercalated cells may also express this gene. Double staining of the principal cell by using a specific antibody such as aquaporin-3 would have been hepful to clarify this point. However, because the population of intercalated cells is very low in IMCD and because the function of arginase II in this cell type will be very difficult to identify, double immunostaining was not performed.
Molecular biology databases reveal that arginase II is a nucleus-encoded enzyme of the mitochondrial matrix composed of 354 amino acid residues and possesses an N-terminal mitochondrial-targeting sequence (Shi et al. 1998). The in vitro synthesis of arginase II precursor allowed the detection of a polypeptide of
40 kDa that can be imported in isolated rat liver mitochondria to process to the mature form of
38 kDa (Gotoh et al. 1996
). The molecular size of 38 kDa for the mature arginase II has been confirmed in mitochondria isolated from kidneys of male and female rats and mice (Levillain et al. 2005
; Levillain et al. 2004
). Regarding the 40-kDa arginase II precursor, it was speculated that the first 22 amino acid residues may correspond to the signal for mitochondrial import. This small peptide sequence is highly conserved in rat and mouse arginase II but differs from that of the human arginase II (see Table 1). However, in the present study, the 40-kDa arginase II was undetectable on Western blot performed with proteins of the cytosolic fractions extracted from either osOM or IM of female rat kidneys. Regarding the subcellular localization of arginase II, our antibody raised against arginase II allows the detection of the 38-kDa mature arginase II almost exclusively in mitochondria of the female rat IMCD and OSPST. Inasmuch as the bulk of the mature arginase II was detected in mitochondria, we hypothesize that the maturation and the import of the 40-kDa arginase II within the mitochondria may occur rapidly after translation. The presence of a low amount of the 38-kDa mature arginase II in the cytosol is quite difficult to explain, unless some mitochondria were injured and broken during the different steps of isolation. In this case, arginase II would have been easily released from the matrix. In contrast, if only a few mitochondria were broken, neither
-subunit F1-ATP synthase, core 2, nor ISP would have been detected in the cytosolic fraction, because these proteins belong to the mitochondrial membrane. Whatever the explanation, our results are in good agreement with those of other authors who reported an arginase II activity in mitochondria isolated from the rat kidney (see review, Jenkinson et al. 1996
).
|
Interestingly, the molecular weight of arginase II deduced from our Western blot is similar in the different renal zones and in mitochondria isolated from rat osOM and IM. This result sustains the view of a single gene of arginase II expressed in the kidney but does not exclude posttranslational modifications leading to arginase II isoforms. At present, the mitochondrial localization of arginase II in the rat IMCD has not been associated with physiological roles and a metabolic pathway.
Physiological Roles of Arginase II in IMCD
The biochemical reaction carried out by arginase II simultaneously decreases the concentration of L-arginine and generates L-ornithine and urea. Consequently, arginase II can be involved in several physiological roles that indisputably make arginase II a renal-associated enzyme. Indeed, the fate of L-arginine and L-ornithine depends on the expression of other enzymes that metabolize these two amino acids. L-ornithine, which is not an end-product of metabolism, plays a pivotal role in two renal metabolic pathways. In the polyamine pathway, ornithine decarboxylase (ODC; EC 4.1.1.17) converts L-ornithine into putrescine, whereas in another reversible metabolic route, the enzyme ornithine aminotransferase (OAT; EC 2.6.1.13) produces L-glutamate and glutamate--semi-aldehyde in the presence of L-ornithine and
-ketoglutarate. In the female and male rat kidneys, ODC gene is expressed in the proximal tubules but not in IMCD (Bettuzzi et al. 1995
; Levillain et al. 2004
), and OAT gene is highly expressed along the entire proximal tubule but poorly expressed in IM (Levillain et al. 2004
). Although no experiments were performed to analyze the fate of L-arginine-derived ornithine in IMCD, it seems plausible that a fraction of L-ornithine can be released into the bloodstream and another fraction metabolized into L-glutamate by the low OAT activity. Because the enzyme glutamate dehydrogenase (GLDH; EC 1.4.1.3) is expressed in IMCD, L-glutamate can be desaminated to produce
-ketoglutarate (Wright and Knepper 1990
). Thereafter,
-ketoglutarate can enter in the citric acid cycle to produce energy during its complete decarboxylation. The pathway is functional in IMCD because the oxidative decarboxylation of L-ornithine has been recently reported in IMCD dissected from the male rat kidneys (Levillain et al. 2004
).
L-arginine is the substrate not only for arginase II but also for other enzymes such as the nitric oxide synthase (NOS; EC 1.14.13.39). Several reports clearly prove that NOS is expressed in the rat IMCD. The highest NOS activity has been found in rat IMCD compared with that of the other nephron segments (Wu et al. 1999). In this report, mRNAs of the neuronal, epithelial, and inducible NOS (nNOS, eNOS, and iNOS, respectively) have been detected in IMCD but not in the pars recta of the proximal tubule. In another study, the highest levels of the three NOS proteins were detected by Western blot in rat IM (Mattson and Higgins 1996
). More recently, NOS2 has been identified in isolated rat IMCD by MALDI-TOF mass spectroscopy (van Balkom et al. 2004
). However, at present, the subcellular localization of the three NOS in IMCD cells remains unknown. Based on the high expression of arginase II and NOS genes in rat IMCD, we hypothesize that arginase II might either regulate NOS or, alternatively, arginase II may be regulated by NOS via the production of NO. Although we have no experiments to support our hypotheses, it is clear that these enzymes used the same substrate, and their high level of expression may be related to an important physiological role in IMCD. Although it is quite difficult to identify the physiological roles of arginase II in each nephron segment expressing this enzyme, a recent report suggests that there is a link between arginase II and NOS in IMCD. Indeed, the infusion of vasopressin to Brattleboro rats simultaneously upregulated the expression of NOS2 and downregulated that of arginase II in IMCD (van Balkom et al. 2004
). In the future, we hope that physiological and pathophysiological studies will offer more insight on the functions of arginase II in the rat kidney.
In conclusion, arginase II gene is expressed in male and female rat IMCD, and the mature arginase II is localized into the mitochondria. Although the physiological roles of arginase II remain to be identified, it is noteworthy that both arginase II and NOS are highly expressed in IMCD.
![]() |
Acknowledgments |
---|
![]() |
Footnotes |
---|
![]() |
Literature Cited |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Bettuzzi S, Marinelli M, Strocchi P, Davalli P, Cevolani D, Corti A (1995) Different localization of spermidine/spermine N1-acetyltransferase and ornithine decarboxylase transcripts in the rat kidney. FEBS Lett 377:321324[CrossRef][Medline]
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248254[CrossRef][Medline]
Bradley MO (1973) Arginase activity patterns and their regulation during embryonic development in liver and kidney. Dev Biol 33:117[CrossRef][Medline]
Dallmann K, Junker H, Balabanov S, Zimmermann U, Giebel J, Walther R (2004) Human agmatinase is diminished in the clear cell type of renal cell carcinoma. Int J Cancer 108:342347[CrossRef][Medline]
Gotoh T, Sonoki T, Nagasaki A, Terada K, Takiguchi M, Mori M (1996) Molecular cloning of cDNA for nonhepatic mitochondrial arginase (arginase II) and comparison of its induction with nitric oxide synthase in a murine macrophage-like cell line. FEBS Lett 395:119122[CrossRef][Medline]
Iyer RK, Bando JM, Jenkinson CP, Vockley JG, Kim PS, Kern RM, Cederbaum SD, et al. (1998) Cloning and characterization of the mouse and rat type II arginase genes. Mol Genet Metab 63:168175[CrossRef][Medline]
Jenkinson CP, Grody WW, Cederbaum SD (1996) Comparative properties of arginases. Comp Biochem Physiol [B] 114:107132[CrossRef][Medline]
Kochakian CD, Stettner CE (1948) Effect of testosterone propionate and growth hormone on the arginase and phosphatases of the organs of the mouse. Am J Physiol 155:262264
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680685[Medline]
Legros F, Chatzoglou E, Frachon P, Ogier De Baulny H, Laforet P, Jardel C, Godinot C, et al. (2001) Functional characterization of novel mutations in the human cytochrome b gene. Eur J Hum Genet 9:510518[CrossRef][Medline]
Levillain O, Hus-Citharel A, Morel F, Bankir L (1989) Production of urea from arginine in pars recta and collecting duct of the rat kidney. Renal Physiol Biochem 12:302312[Medline]
Levillain O, Hus-Citharel A (1996) Distribution of arginase along the mammalian nephron. In De Deyn PP, Marescau B, Qureshi IA, Mori A, eds. Guanidino Compounds: 2. London, John Libbey & Company, Ltd. 7785
Levillain O, Balvay S, Peyrol S (2005) Localization and differential expression of arginase II in male and female mouse kidney. Pflugers Archiv 449:491503[CrossRef][Medline]
Levillain O, Hus-Citharel A, Garvi S, Peyrol S, Reymond I, Mutin M, Morel F (2004) Ornithine metabolism in male and female rat kidney mitochondrial expression of ornithine aminotransferase and arginase II. Am J Physiol Renal Physiol 286:F727F738
Lortie MJ, Novotny WF, Peterson OW, Vallon V, Malvey K, Mendonca M, Satriano J, et al. (1996) Agmatine, a bioactive metabolite of arginine. Production, degradation, and functional effects in the kidney of the rat. J Clin Invest 97:413420
Manteuffel-Cymborowska M, Chmurzynska W, Peska M, Grzelakowska-Sztabert B (1995) Arginine and ornithine metabolizing enzymes in testosterone-induced hypertrophic mouse kidney. Int J Biochem Cell Biol 27:287295[CrossRef][Medline]
Mattson DL, Higgins DJ (1996) Influence of dietary sodium intake on renal medullary nitric oxide synthase. Hypertension 27:688692
Miyanaka K, Gotoh T, Nagasaki A, Takeya M, Ozaki M, Iwase K, Takiguchi M, et al. (1998) Immunohistochemistry localization of arginase II and other enzymes of arginine metabolism in rat kidney and liver. Histochem J 30:741751[CrossRef][Medline]
Moradi-Ameli M, Godinot C (1983) Characterization of monoclonal antibodies against mitochondrial F1-ATPase. Proc Natl Acad Sci USA 80:61676171[Abstract]
Morris SM Jr, Bhamidipati D, Kepka-Lenhart D (1997) Human type II arginase: sequence analysis and tissue-specific expression. Gene 193:157161[CrossRef][Medline]
Morrissey J, McCracken R, Ishidoya S, Klahr S (1995) Partial cloning and characterization of an arginine decarboxylase in the kidney. Kidney Int 47:14581461[Medline]
Ozaki M, Gotoh T, Nagasaki A, Miyanaka K, Takeya M, Fujiyama S, Tomita K, et al. (1999) Expression of arginase II and related enzymes in the rat small intestine and kidney. J Biochem Tokyo 125:586593[Abstract]
Pfaller W (1982) Structure function correlation on rat kidney. Quantitative correlation of structure and function in the normal and injured rat kidney. In Hild W, Van Limborgh J, Ortmann R, Pauly JE, Schiebler TH, eds. Advances in Anatomy Embryology and Cell Biology, vol. 70. Berlin, Springer-Verlag, 1106
Reymond I, Bitoun M, Levillain O, Tappaz M (2000) Regional expression and histological localization of cysteine sulfate decarboxylase mRNA in the rat kidney. J Histochem Cytochem 48:14611468
Robinson RR, Schmidt-Nielsen B (1963) Distribution of arginase within the kidneys of several vertebrate species. J Cell Comp Physiol 62:147157[CrossRef]
Sands JM, Terada Y, Bernard LM, Knepper MA (1989) Aldose reductase activities in microdissected rat renal tubule segments. Am J Physiol 256:F563F569[Medline]
Shi O, Kepka-Lenhart D, Morris SM Jr, O'Brien WE (1998) Structure of the murine arginase II gene. Mamm Genome 9:822824[CrossRef][Medline]
Skrzypek-Osiecka I, Robin Y, Porembska Z (1983) Purification of rat kidney arginases A1 and A4 and their subcellular distribution. Acta Biochim Pol 30:8392[Medline]
Tisher CC, Madsen KM (2000) Anatomy of the kidney. In Brenner BM, ed. The Kidney. Philadelphia, WB Saunders, 367
van Balkom BW, Hoffert JD, Chou CL, Knepper MA (2004) Proteomic analysis of long-term vasopressin action in the inner medullary collecting duct of the Brattleboro rat. Am J Physiol Renal Physiol 286:F216F224
Wright PA, Knepper MA (1990) Glutamate dehydrogenase activities in microdissected rat nephron segments: effects of acid-base loading. Am J Physiol 259:F53F59[Medline]
Wu F, Park F, Cowley AW, Mattson DL (1999) Quantification of nitric oxide synthase activity in microdissected segments of the rat kidney. Am J Physiol Renal Physiol 45:F874F881
Yu H, Yoo PK, Aguirre CC, Tsoa RW, Kern RM, Grody WW, Cederbaum SD, et al. (2003) Widespread expression of arginase I in mouse tissues. Biochemical and physiological implications. J Histochem Cytochem 51:11511160