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Article ; Online: Aging Increases Hypoxia-Induced Endothelial Permeability and Blood-Brain Barrier Dysfunction by Upregulating Arginase-II.

Cheng, Xin / Potenza, Duilio M / Brenna, Andrea / Ajalbert, Guillaume / Yang, Zhihong / Ming, Xiu-Fen

2024

Abstract: Increased endothelial permeability plays an important role in blood-brain barrier (BBB) dysfunction and is implicated in neuronal injury in many diseased conditions. BBB disruption is primarily determined by dysfunction of endothelial cell-cell junctions. ...

Abstract	Increased endothelial permeability plays an important role in blood-brain barrier (BBB) dysfunction and is implicated in neuronal injury in many diseased conditions. BBB disruption is primarily determined by dysfunction of endothelial cell-cell junctions. Deprivation of oxygen supply or hypoxia, a common feature of a variety of human diseases, is a major risk factor for BBB disruption. The molecular regulatory mechanisms of hypoxia-induced BBB dysfunction remain incompletely understood. The mitochondrial enzyme, arginase type II (Arg-II), has been shown to promote endothelial dysfunction. However, its role in hypoxia-induced BBB dysfunction has not been explored. In the C57BL/6J mouse model, hypoxia (8% O
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2625789-0
ISSN	2152-5250 ; 2152-5250
ISSN (online)	2152-5250
ISSN	2152-5250
DOI	10.14336/AD.2023.1225
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Elevation of Arginase-II in Podocytes Contributes to Age-Associated Albuminuria in Male Mice.

Ajalbert, Guillaume / Brenna, Andrea / Ming, Xiu-Fen / Yang, Zhihong / Potenza, Duilio M

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: One of the manifestations of renal aging is podocyte dysfunction and loss, which are associated with proteinuria and glomerulosclerosis. Studies show a male bias in glomerular dysfunction and chronic kidney diseases, and the underlying mechanisms remain ... ...

Abstract	One of the manifestations of renal aging is podocyte dysfunction and loss, which are associated with proteinuria and glomerulosclerosis. Studies show a male bias in glomerular dysfunction and chronic kidney diseases, and the underlying mechanisms remain obscure. Recent studies demonstrate the role of an age-associated increase in arginase-II (Arg-II) in proximal tubules of both male and female mice. However, it is unclear whether Arg-II is also involved in aging glomeruli. The current study investigates the role of the sex-specific elevation of Arg-II in podocytes in age-associated increased albuminuria. Young (3-4 months) and old (20-22 months) male and female mice of
MeSH term(s)	Animals ; Female ; Male ; Mice ; Albuminuria/metabolism ; Arginase/genetics ; Arginase/metabolism ; Kidney Glomerulus/metabolism ; Podocytes/metabolism ; Proteinuria/metabolism
Chemical Substances	Arginase (EC 3.5.3.1)
Language	English
Publishing date	2023-07-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241311228
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Article ; Online: Role of pulmonary epithelial arginase-II in activation of fibroblasts and lung inflammaging.

Zhu, Cui / Potenza, Duilio M / Yang, Yang / Ajalbert, Guillaume / Mertz, Kirsten D / von Gunten, Stephan / Ming, Xiu-Fen / Yang, Zhihong

Aging cell

2023 Volume 22, Issue 4, Page(s) e13790

Abstract: Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our ... ...

Abstract	Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our present study shows increased Arg-II levels in aging lung of female mice, which is detected in bronchial ciliated epithelium, club cells, alveolar type 2 (AT2) pneumocytes, and fibroblasts (but not vascular endothelial and smooth muscle cells). Similar cellular localization of Arg-II is also observed in human lung biopsies. The age-associated increase in lung fibrosis and inflammatory cytokines, including IL-1β and TGF-β1 that are highly expressed in bronchial epithelium, AT2 cells, and fibroblasts, are ameliorated in arg-ii deficient (arg-ii
MeSH term(s)	Male ; Female ; Mice ; Humans ; Animals ; Transforming Growth Factor beta1/metabolism ; Arginase/genetics ; Arginase/metabolism ; Lung/pathology ; Cytokines/metabolism ; Fibroblasts/metabolism ; Fibrosis
Chemical Substances	Transforming Growth Factor beta1 ; Arginase (EC 3.5.3.1) ; Cytokines
Language	English
Publishing date	2023-02-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.13790
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Article ; Online: Paracrine Effects of Renal Proximal Tubular Epithelial Cells on Podocyte Injury under Hypoxic Conditions Are Mediated by Arginase-II and TGF-β1.

Ma, Yiqiong / Potenza, Duilio Michele / Ajalbert, Guillaume / Brenna, Andrea / Zhu, Cui / Ming, Xiu-Fen / Yang, Zhihong

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Hypoxia is an important risk for renal disease. The mitochondrial enzyme arginase-II (Arg-II) is expressed and/or induced by hypoxia in proximal tubular epithelial cells (PTECs) and in podocytes, leading to cellular damage. Because PTECs are vulnerable ... ...

Abstract	Hypoxia is an important risk for renal disease. The mitochondrial enzyme arginase-II (Arg-II) is expressed and/or induced by hypoxia in proximal tubular epithelial cells (PTECs) and in podocytes, leading to cellular damage. Because PTECs are vulnerable to hypoxia and located in proximity to podocytes, we examined the role of Arg-II in the crosstalk of PTECs under hypoxic conditions with podocytes. A human PTEC cell line (HK2) and a human podocyte cell line (AB8/13) were cultured.
MeSH term(s)	Humans ; Apoptosis ; Arginase/metabolism ; Epithelial Cells/metabolism ; Kidney Tubules, Proximal/metabolism ; Paracrine Communication/genetics ; Podocytes/metabolism ; Podocytes/pathology ; Transforming Growth Factor beta1/metabolism
Chemical Substances	Arginase (EC 3.5.3.1) ; Transforming Growth Factor beta1
Language	English
Publishing date	2023-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043587
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Article ; Online: Inhibition of p38mapk Reduces Adipose Tissue Inflammation in Aging Mediated by Arginase-II.

Huang, Ji / Liu, Chang / Ming, Xiu-Fen / Yang, Zhihong

Pharmacology

2020 Volume 105, Issue 9-10, Page(s) 491–504

Abstract: Background: Adipose tissue inflammation occurs not only in obesity but also in aging and is mechanistically linked with age-associated diseases. Studies show that ablation of the l-arginine-metabolizing enzyme arginase-II (Arg-II) reduces adipose tissue ...

Abstract	Background: Adipose tissue inflammation occurs not only in obesity but also in aging and is mechanistically linked with age-associated diseases. Studies show that ablation of the l-arginine-metabolizing enzyme arginase-II (Arg-II) reduces adipose tissue inflammation and improves glucose tolerance in obesity. However, the role of Arg-II in aging adipose tissue inflammation is not clear. Objective: This study investigated the role of Arg-II in age-associated adipose tissue inflammation. Methods: Visceral adipose tissues of young (3-6 months) and old (20-24 months) wild-type (WT) and Arg-II-/- mice were investigated. Immunofluorescence confocal microscopy was performed for analysis of macrophage accumulation and cellular localization of arginase and cytokines; expression of arginase and cytokines was analyzed by qRT-PCR or immunoblotting or ELISA; activation of mitogen-activated protein kinases in adipose tissues was analyzed by immunoblotting; and arginase activity was measured by colorimetric determination of urea production. Results: In the old WT mice, there is more macrophage accumulation in the visceral adipose tissues than in Arg-II knockout animals. An age-associated increase in arginase activity and Arg-II expression in adipose tissues of WT mice is observed. Arg-II knockout enhances Arg-I expression and activity, but inhibits interleukin (IL)-6 expression and secretion and reduces active p38mapk in aging adipose tissue macrophages and stromal cells. Treatment of aging adipose tissues of WT mice with a specific p38mapk inhibitor SB203580 reduces IL-6 secretion. Conclusions: Arg-II promotes IL-6 production in aging adipose tissues through p38mapk. The results suggest that targeting Arg-II or inhibiting p38mapk could be beneficial in reducing age-associated adipose tissue inflammation.
MeSH term(s)	Adipose Tissue/chemistry ; Adipose Tissue/metabolism ; Aging/metabolism ; Animals ; Arginase/genetics ; Arginase/metabolism ; Female ; Inflammation/complications ; Inflammation/metabolism ; Interleukin-6/metabolism ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications ; Obesity/metabolism ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	Interleukin-6 ; interleukin-6, mouse ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Arg1 protein, mouse (EC 3.5.3.1) ; Arg2 protein, mouse (EC 3.5.3.1) ; Arginase (EC 3.5.3.1)
Language	English
Publishing date	2020-05-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	206671-3
ISSN	1423-0313 ; 0031-7012
ISSN (online)	1423-0313
ISSN	0031-7012
DOI	10.1159/000507635
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Detrimental Effects of Chronic L-Arginine Rich Food on Aging Kidney.

Huang, Ji / Ladeiras, Diogo / Yu, Yi / Ming, Xiu-Fen / Yang, Zhihong

Frontiers in pharmacology

2021 Volume 11, Page(s) 582155

Abstract: The impaired L-arginine/nitric oxide pathway is a well-recognized mechanism for cardiovascular and renal diseases with aging. Therefore, supplementation of L-arginine is widely proposed to boost health or as adjunct therapy for the patients. However, ... ...

Abstract	The impaired L-arginine/nitric oxide pathway is a well-recognized mechanism for cardiovascular and renal diseases with aging. Therefore, supplementation of L-arginine is widely proposed to boost health or as adjunct therapy for the patients. However, clinical data, show adverse effects and even enhanced mortality in patients receiving long-term L-arginine supplementation. The effects of long-term L-arginine supplementation on kidney aging and the underlying mechanisms remain elusive. Moreover, high protein and high amino acid diet has been thought detrimental for kidney. We therefore investigated effects of chronic dietary L-arginine supplementation on kidney aging. In both young (4 months) and old (18-24 months) mice, animals either receive standard chow containing 0.65% L-arginine or diet supplemented with L-arginine to 2.46% for 16 weeks. Inflammation and fibrosis markers and albuminuria are then analyzed. Age-associated increases in
Language	English
Publishing date	2021-01-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.582155
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Article: Role of tubular epithelial arginase-II in renal inflammaging.

Huang, Ji / Liang, Xiujie / Ladeiras, Diogo / Fellay, Benoit / Ming, Xiu-Fen / Yang, Zhihong

NPJ aging and mechanisms of disease

2021 Volume 7, Issue 1, Page(s) 5

Abstract: The aging kidney undergoes complex changes and is vulnerable to injury and development of chronic kidney disease (CKD) with preponderance affecting more women than men. Evidence has been presented that the type-II L-arginine:ureohydrolase, arginase-II ( ... ...

Abstract	The aging kidney undergoes complex changes and is vulnerable to injury and development of chronic kidney disease (CKD) with preponderance affecting more women than men. Evidence has been presented that the type-II L-arginine:ureohydrolase, arginase-II (Arg-II) plays a role in the acceleration of aging. Arg-II is highly expressed in the kidney. However, the role of Arg-II in renal aging is not known. This study is to investigate whether Arg-II is involved in the kidney aging process dependently on sex. Arg-II level in the kidney of wild type (WT) mice is significantly elevated with aging, which is accompanied by an increase in expression of the inflammatory cytokines/chemokines, tissue macrophages, factors involved in fibrosis, and tubulointestitial fibrosis in both males and females. This renal aging phenotype is significantly suppressed in arg-II
Language	English
Publishing date	2021-03-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2836493-4
ISSN	2056-3973
ISSN	2056-3973
DOI	10.1038/s41514-021-00057-8
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Article ; Online: Role of Arginase-II in Podocyte Injury under Hypoxic Conditions.

Ren, Zhilong / Potenza, Duilio Michele / Ma, Yiqiong / Ajalbert, Guillaume / Hoogewijs, David / Ming, Xiu-Fen / Yang, Zhihong

Biomolecules

2022 Volume 12, Issue 9

Abstract: Hypoxia plays a crucial role in acute and chronic renal injury, which is attributable to renal tubular and glomerular cell damage. Some studies provide evidence that hypoxia-dependent upregulation of the mitochondrial enzyme arginase type-II (Arg-II) in ... ...

Abstract	Hypoxia plays a crucial role in acute and chronic renal injury, which is attributable to renal tubular and glomerular cell damage. Some studies provide evidence that hypoxia-dependent upregulation of the mitochondrial enzyme arginase type-II (Arg-II) in tubular cells promotes renal tubular injury. It is, however, not known whether Arg-II is also expressed in glomerular cells, particularly podocytes under hypoxic conditions, contributing to hypoxia-induced podocyte injury. The effects of hypoxia on human podocyte cells (AB8/13) in cultures and on isolated kidneys from wild-type (
MeSH term(s)	Actins/metabolism ; Albuminuria ; Animals ; Arginase/genetics ; Arginase/metabolism ; Humans ; Hypoxia/metabolism ; Mice ; Podocytes/metabolism ; Prolyl Hydroxylases/metabolism ; Prolyl Hydroxylases/pharmacology ; Reactive Oxygen Species/metabolism ; Rotenone/pharmacology
Chemical Substances	Actins ; Reactive Oxygen Species ; Rotenone (03L9OT429T) ; Prolyl Hydroxylases (EC 1.14.11.-) ; ARG2 protein, human (EC 3.5.3.1) ; Arg2 protein, mouse (EC 3.5.3.1) ; Arginase (EC 3.5.3.1)
Language	English
Publishing date	2022-08-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12091213
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Article: Hypoxia Enhances Endothelial Intercellular Adhesion Molecule 1 Protein Level Through Upregulation of Arginase Type II and Mitochondrial Oxidative Stress.

Liang, Xiujie / Arullampalam, Prakash / Yang, Zhihong / Ming, Xiu-Fen

Frontiers in physiology

2019 Volume 10, Page(s) 1003

Abstract: Hypoxia plays a crucial role in the pathogenesis of cardiovascular diseases. Mitochondrial enzyme arginase type II (Arg-II) is reported to lead to endothelial dysfunction and enhance the expression of endothelial inflammatory adhesion molecules such as ... ...

Abstract	Hypoxia plays a crucial role in the pathogenesis of cardiovascular diseases. Mitochondrial enzyme arginase type II (Arg-II) is reported to lead to endothelial dysfunction and enhance the expression of endothelial inflammatory adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In this study, we investigate the role of Arg-II in hypoxia-induced endothelial activation and the potential underlying mechanisms. Exposure of the human endothelial cells to hypoxia induced a time-dependent increase in Arg-II, HIF1α, HIF2α, and ICAM-1 protein level, whereas no change in the protein level of VCAM-1 and E-selectin was observed. Similar effects were obtained in cells treated with a
Language	English
Publishing date	2019-08-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2019.01003
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Article: Functions of arginase isoforms in macrophage inflammatory responses: impact on cardiovascular diseases and metabolic disorders.

Yang, Zhihong / Ming, Xiu-Fen

Frontiers in immunology

2014 Volume 5, Page(s) 533

Abstract: Macrophages play a paramount role in immunity and inflammation-associated diseases, including infections, cardiovascular diseases, obesity-associated metabolic imbalances, and cancer. Compelling evidence from studies of recent years demonstrates that ... ...

Abstract	Macrophages play a paramount role in immunity and inflammation-associated diseases, including infections, cardiovascular diseases, obesity-associated metabolic imbalances, and cancer. Compelling evidence from studies of recent years demonstrates that macrophages are heterogeneous and undergo heterogeneous phenotypic changes in response to microenvironmental stimuli. The M1 killer type response and the M2 repair type response are best known, and are two extreme examples. Among other markers, inducible nitric oxide synthase and type-I arginase (Arg-I), the enzymes that are involved in l-arginine/nitric oxide (NO) metabolism, are associated with the M1 and M2 phenotype, respectively, and therefore widely used as the markers for characterization of the two macrophage phenotypes. There is also a type-II arginase (Arg-II), which is expressed in macrophages and prevalently viewed as having the same function as Arg-I in the cells. In contrast to Arg-I, little information on the role of Arg-II in macrophage inflammatory responses is available. Emerging evidence, however, suggests that differential roles of Arg-I and Arg-II in regulating macrophage functions. In this article, we will review recent developments on the functional roles of the two arginase isoforms in regulation of macrophage inflammatory responses by focusing on their impact on the pathogenesis of cardiovascular diseases and metabolic disorders.
Language	English
Publishing date	2014
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2014.00533
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