Université de Fribourg

Inhibition of p38mapk reduces adipose tissue inflammation in aging mediated by arginase-II

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

In: Pharmacology, 2020, vol. 105, no. 9–10, p. 491–504

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....

Université de Fribourg

Arginase‐II promotes melanoma migration and adhesion through enhancing hydrogen peroxide production and STAT3 signaling

Yu, Yi ; Ladeiras, Diogo ; Xiong, Yuyan ; Boligan, Kayluz Frias ; Liang, Xiujie ; Gunten, Stephan ; Hunger, Robert E. ; Ming, Xiu‐Fen ; Yang, Zhihong

In: Journal of Cellular Physiology, 2020, p. jcp.29814

Elevated arginase type II (Arg‐II) associates with higher grade tumors. Its function and underlying molecular mechanisms in melanoma remain elusive. In the present study, we observed a significantly higher frequency of Arg‐II expression in melanoma of patients with metastasis than those without metastasis. Silencing Arg‐II in two human melanoma cell lines slowed down the cell growth,...

Université de Fribourg

Myosin 1b regulates nuclear AKT activation by preventing localization of PTEN in the nucleus

Yu, Yi ; Xiong, Yuyan ; Ladeiras, Diogo ; Yang, Zhihong ; Ming, Xiu-Fen

In: iScience, 2019, vol. 19, p. 39–53

Insulin-induced AKT activation is dependent on phosphoinositide 3-kinase and opposed by tumor suppressor phosphatase and tensin homolog (PTEN). Our previous study demonstrates that myosin 1b (MYO1B) mediates arginase-II-induced activation of mechanistic target of rapamycin complex 1 that is regulated by AKT. However, the role of MYO1B in AKT activation is unknown. Here we show that silencing...

Université de Fribourg

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

In: Frontiers in Physiology, 2019, vol. 10, p. -

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...

Université de Fribourg

Kidney mass reduction leads to L‐arginine metabolism‐dependent blood pressure increase in mice

Muralidharan Pillai, Samyuktha ; Seebeck, Petra ; Fingerhut, Ralph ; Huang, Ji ; Ming, Xiu‐Fen ; Yang, Zhihong ; Verrey, François

In: Journal of the American Heart Association, 2018, vol. 7, no. 5, p. e008025

Background Uninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of L‐arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts L‐arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice. Methods and Results In a first series of experiments, we observed...

Université de Fribourg

Arginase-II activates mTORC1 through myosin-1b in vascular cell senescence and apoptosis

Yu, Yi ; Xiong, Yuyan ; Montani, Jean-Pierre ; Yang, Zhihong ; Ming, Xiu-Fen

In: Cell Death & Disease, 2018, vol. 9, no. 3, p. 313

Type-II L-arginine:ureahydrolase, arginase-II (Arg-II), is shown to activate mechanistic target of rapamycin complex 1 (mTORC1) pathway and contributes to cell senescence and apoptosis. In an attempt to elucidate the underlying mechanism, we identified myosin-1b (Myo1b) as a mediator. Overexpression of Arg-II induces re-distribution of lysosome and mTOR but not of tuberous sclerosis complex...

Université de Fribourg

Arginase-ii deficiency extends lifespan in mice

Xiong, Yuyan ; Yepuri, Gautham ; Montani, Jean-Pierre ; Ming, Xiu-Fen ; Yang, Zhihong

In: Frontiers in Physiology, 2017, vol. 8, p. -

The mitochondrial arginase type II (Arg-II) has been shown to interact with ribosomal protein S6 kinase 1 (S6K1) and mitochondrial p66Shc and to promote cell senescence, apoptosis and inflammation under pathological conditions. However, the impact of Arg-II on organismal lifespan is not known. In this study, we demonstrate a significant lifespan extension in mice with Arg-II gene deficiency...

Université de Fribourg

Arginase-II promotes tumor necrosis Factor-α release from pancreatic acinar cells causing β-cell apoptosis in aging

Xiong, Yuyan ; Yepuri, Gautham ; Necetin, Sevil ; Montani, Jean-Pierre ; Ming, Xiu-Fen ; Yang, Zhihong

In: Diabetes, 2017, vol. 66, no. 6, p. 1636–1649

Aging is associated with glucose intolerance. Arginase-II (Arg-II), the type-II L-arginine- ureahydrolase, is highly expressed in pancreas. However, its role in regulation of pancreatic β-cell function is not known. Here we show that female (not male) mice deficient in Arg-II (Arg-II−/−) are protected from age-associated glucose intolerance and reveal greater glucose induced-insulin...

Université de Fribourg

Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression

Reiner, Martin F. ; Akhmedov, Alexander ; Stivala, Simona ; Keller, Stephan ; Gaul, Daniel S. ; Bonetti, Nicole R. ; Savarese, Gianluigi ; Glanzmann, Martina ; Zhu, Cuicui ; Ruf, Wolfram ; Yang, Zhihong ; Matter, Christian M. ; Lüscher, Thomas F. ; Camici, Giovanni G. ; Beer, Juerg H.

In: Cardiovascular Research, 2017, vol. 113, no. 1, p. 61–69

The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been...

Université de Fribourg

Genetic targeting of arginase-ii in mouse prevents renal oxidative stress and inflammation in diet-induced obesity

Huang, Ji ; Rajapakse, Angana ; Xiong, Yuyan ; Montani, Jean-Pierre ; Verrey, François ; Ming, Xiu-Fen ; Yang, Zhihong

In: Frontiers in Physiology, 2016, vol. 7, p. -

Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L- arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase- II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and...