Renal tubular arginase-2 participates in the formation of the corticomedullary urea gradient and attenuates kidney damage in ischemia-reperfusion injury in mice.
arginase-2
arginine
kidney
kidney injury
proximal tubule
urea
Journal
Acta physiologica (Oxford, England)
ISSN: 1748-1716
Titre abrégé: Acta Physiol (Oxf)
Pays: England
ID NLM: 101262545
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
09
12
2019
revised:
17
02
2020
accepted:
18
02
2020
pubmed:
20
2
2020
medline:
27
7
2021
entrez:
20
2
2020
Statut:
ppublish
Résumé
Arginase 2 (ARG2) is a mitochondrial enzyme that catalyses hydrolysis of l-arginine into urea and l-ornithine. In the kidney, ARG2 is localized to the S3 segment of the proximal tubule. It has been shown that expression and activity of this enzyme are upregulated in a variety of renal pathologies, including ischemia-reperfusion (IR) injury. However, the (patho)physiological role of ARG2 in the renal tubule remains largely unknown. We addressed this question in mice with conditional knockout of Arg2 in renal tubular cells (Arg2 We demonstrate that cKO mice exhibit impaired urea concentration and osmolality gradients along the corticomedullary axis. In a model of unilateral ischemia-reperfusion injury (UIRI) with an intact contralateral kidney, ischemia followed by 24 hours of reperfusion resulted in significantly more pronounced histological damage in ischemic kidneys from cKO mice compared to control and sham-operated mice. In parallel, UIRI-subjected cKO mice exhibited a broad range of renal functional abnormalities, including albuminuria and aminoaciduria. Fourteen days after UIRI, the cKO mice exhibited complex phenotype characterized by significantly lower body weight, increased plasma levels of early predictive markers of kidney disease progression (asymmetric dimethylarginine and symmetric dimethylarginine), impaired mitochondrial function in the ischemic kidney but no difference in kidney fibrosis as compared to control mice. Collectively, these results establish the role of ARG2 in the formation of corticomedullary urea and osmolality gradients and suggest that this enzyme attenuates kidney damage in ischemia-reperfusion injury.
Substances chimiques
Urea
8W8T17847W
Arg2 protein, mouse
EC 3.5.3.1
Arginase
EC 3.5.3.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13457Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
Références
Ochocki JD, Khare S, Hess M, et al. Arginase 2 suppresses renal carcinoma progression via biosynthetic cofactor pyridoxal phosphate depletion and increased polyamine toxicity. Cell Metab. 2018;27(6):1263-1280.e1266.
Zaytouni T, Tsai PY, Hitchcock DS, et al. Critical role for arginase 2 in obesity-associated pancreatic cancer. Nat Commun. 2017;8(1):242.
Xu W, Ghosh S, Comhair SA, et al. Increased mitochondrial arginine metabolism supports bioenergetics in asthma. J Clin Invest. 2016;126(7):2465-2481.
Ryoo S, Gupta G, Benjo A, et al. Endothelial arginase II: a novel target for the treatment of atherosclerosis. Circ Res. 2008;102(8):923-932.
Zhang Y, Higgins CB, Fortune HM, et al. Hepatic arginase 2 (Arg2) is sufficient to convey the therapeutic metabolic effects of fasting. Nat Commun. 2019;10(1):1587.
Suwanpradid J, Rojas M, Behzadian MA, Caldwell RW, Caldwell RB. Arginase 2 deficiency prevents oxidative stress and limits hyperoxia-induced retinal vascular degeneration. PLoS ONE. 2014;9(11):e110604.
Caldwell RW, Rodriguez PC, Toque HA, Narayanan SP, Caldwell RB. Arginase: a multifaceted enzyme important in health and disease. Physiol Rev. 2018;98(2):641-665.
Levillain O, Hus-Citharel A, Morel F, Bankir L. Localization of arginine synthesis along rat nephron. Am J Physiol. 1990;259(6 Pt 2):F916-F923.
Levillain O, Hus-Citharel A, Morel F, Bankir L. Production of urea from arginine in pars recta and collecting duct of the rat kidney. Renal Physiol Biochem. 1989;12(5-6):302-312.
Levillain O, Hus-Citharel A, Morel F, Bankir L. Localization of urea and ornithine production along mouse and rabbit nephrons: functional significance. Am J Physiol. 1992;263(5 Pt 2):F878-F885.
Levillain O, Hus-Citharel A, Garvi S, et al. Ornithine metabolism in male and female rat kidney: mitochondrial expression of ornithine aminotransferase and arginase II. Am J Physiol Renal Physiol. 2004;286(4):F727-F738.
Weinberg JM, Venkatachalam MA, Roeser NF, et al. Anaerobic and aerobic pathways for salvage of proximal tubules from hypoxia-induced mitochondrial injury. Am J Physiol Renal Physiol. 2000;279(5):F927-F943.
Weinberg JM, Venkatachalam MA, Roeser NF, Nissim I. Mitochondrial dysfunction during hypoxia/reoxygenation and its correction by anaerobic metabolism of citric acid cycle intermediates. Proc Natl Acad Sci USA. 2000;97(6):2826-2831.
Raup-Konsavage WM, Gao T, Cooper TK, Morris SM Jr, Reeves WB, Awad AS. Arginase-2 mediates renal ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2017;313(2):F522-F534.
Morris SM Jr, Gao T, Cooper TK, Kepka-Lenhart D, Awad AS. Arginase-2 mediates diabetic renal injury. Diabetes. 2011;60(11):3015-3022.
Romero MJ, Yao L, Sridhar S, et al. l-citrulline protects from kidney damage in type 1 diabetic mice. Front Immunol. 2013;4:480.
Akomolafe SF, Akinyemi AJ, Anadozie SO. Phenolic acids (gallic and tannic acids) modulate antioxidant status and cisplatin induced nephrotoxicity in rats. Int Scholarly Res Not. 2014;2014:984709.
Lacroix C, Caubet C, Gonzalez-de-Peredo A, et al. Label-free quantitative urinary proteomics identifies the arginase pathway as a new player in congenital obstructive nephropathy. Mol Cell Proteomics. 2014;13(12):3421-3434.
Levillain O. Expression and function of arginine-producing and consuming-enzymes in the kidney. Amino Acids. 2012;42(4):1237-1252.
Huang J, Montani JP, Verrey F, Feraille E, Ming XF, Yang Z. Arginase-II negatively regulates renal aquaporin-2 and water reabsorption. FASEB J. 2018;32(10):5520-5531.
Kochakian CD. The effect of dose and nutritive state on kidney arginase after steroid stimulation. J Biol Chem. 1945;161:115-125.
Dounce AL, Beyer GT. The arginase activity of isolated cell nuclei. J Biol Chem. 1948;174(3):859-872.
Nikolaeva S, Ansermet C, Centeno G, et al. Nephron-specific deletion of circadian clock gene Bmal1 alters the plasma and renal metabolome and impairs drug disposition. J Am Soc Nephrol. 2016;27(10):2997-3004.
Brezis M, Agmon Y, Epstein FH. Determinants of intrarenal oxygenation. I. Effects of diuretics. Am J Physiol. 1994;267(6 Pt 2):F1059-F1062.
Liu J, Kumar S, Dolzhenko E, et al. Molecular characterization of the transition from acute to chronic kidney injury following ischemia/reperfusion. JCI Insight. 2017;2(18):e94716.
Le Clef N, Verhulst A, D'Haese PC, Vervaet BA. Unilateral renal ischemia-reperfusion as a robust model for acute to chronic kidney injury in mice. PLoS ONE. 2016;11(3):e0152153.
Hall AM, Unwin RJ. The not so 'mighty chondrion': emergence of renal diseases due to mitochondrial dysfunction. Nephron Physiol. 2007;105(1):p1-p10.
Emrich IE, Zawada AM, Martens-Lobenhoffer J, et al. Symmetric dimethylarginine (SDMA) outperforms asymmetric dimethylarginine (ADMA) and other methylarginines as predictor of renal and cardiovascular outcome in non-dialysis chronic kidney disease. Clin Res Cardiol. 2018;107(3):201-213.
Betz B, Moller-Ehrlich K, Kress T, et al. Increased symmetrical dimethylarginine in ischemic acute kidney injury as a causative factor of renal L-arginine deficiency. Transl Res. 2013;162(2):67-76.
Teerlink T, Luo Z, Palm F, Wilcox CS. Cellular ADMA: regulation and action. Pharmacol Res. 2009;60(6):448-460.
Nakayama Y, Ueda S, Yamagishi S, et al. Asymmetric dimethylarginine accumulates in the kidney during ischemia/reperfusion injury. Kidney Int. 2014;85(3):570-578.
Hall AM, Schuh CD. Mitochondria as therapeutic targets in acute kidney injury. Curr Opin Nephrol Hypertens. 2016;25(4):355-362.
Huang J, Rajapakse A, Xiong Y, et al. Genetic targeting of arginase-II in mouse prevents renal oxidative stress and inflammation in diet-induced obesity. Front Physiol. 2016;7:560.
Traykova-Brauch M, Schonig K, Greiner O, et al. An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice. Nat Med. 2008;14(9):979-984.
Kepka-Lenhart D, Ash DE, Morris SM. Determination of mammalian arginase activity. Methods Enzymol. 2008;440:221-230.
Eisner C, Faulhaber-Walter R, Wang Y, et al. Major contribution of tubular secretion to creatinine clearance in mice. Kidney Int. 2010;77(6):519-526.
Qi Z, Whitt I, Mehta A, et al. Serial determination of glomerular filtration rate in conscious mice using FITC-inulin clearance. Am J Physiol Renal Physiol. 2004;286(3):F590-F596.