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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

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...

Université de Fribourg

"En Face" detection of nitric oxide and superoxide in endothelial layer of intact arteries

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

In: Journal of Visualized Experiments, 2016, no. 108, p. -

Endothelium-derived nitric oxide (NO) produced from endothelial NO-synthase (eNOS) is one of the most important vasoprotective molecules in cardiovascular physiology. Dysfunctional eNOS such as uncoupling of eNOS leads to decrease in NO bioavailability and increase in superoxide anion (O₂.−) production, and in turn promotes cardiovascular diseases. Therefore, appropriate...

Université de Fribourg

Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation

Liu, Chang ; Rajapakse, Angana G. ; Riedo, Erwin ; Fellay, Benoit ; Bernhard, Marie-Claire ; Montani, Jean-Pierre ; Yang, Zhihong ; Ming, Xiu-Fen

In: Scientific Reports, 2016, vol. 6, p. 20405

Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in...

Université de Fribourg

P38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity

Yu, Yi ; Rajapakse, Angana G. ; Montani, Jean-Pierre ; Yang, Zhihong ; Ming, Xiu-Fen

In: Cardiovascular Diabetology, 2014, vol. 13, no. 1, p. 113

Background Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk...

Université de Fribourg

Arginase: the emerging therapeutic target for vascular oxidative stress and inflammation

Yang, Zhihong ; Ming, Xiu-Fen

In: Frontiers in Inflammation, 2013, vol. 4, p. 149

Oxidative stress and inflammation in the vascular wall are essential mechanisms of atherosclerosis and vascular dysfunctions associated with risk factors such as metabolic diseases, aging, hypertension, etc. Evidence has been provided that activation of the vascular endothelial cells in the presence of the risk factors promotes oxidative stress and vascular inflammatory responses, leading to...