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

Arginase‐II induces vascular smooth muscle cell senescence and apoptosis through p66Shc and p53 independently of its l‐arginine ureahydrolase activity: implications for atherosclerotic plaque vulnerability

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

In: Journal of the American Heart Association, 2013, vol. 2, no. 4, p. e000096

Background Vascular smooth muscle cell (VSMC) senescence and apoptosis are involved in atherosclerotic plaque vulnerability. Arginase‐II (Arg‐II) has been shown to promote vascular dysfunction and plaque vulnerability phenotypes in mice through uncoupling of endothelial nitric oxide synthase and activation of macrophage inflammation. The function of Arg‐II in VSMCs with respect to plaque...

Université de Fribourg

Positive crosstalk between arginase-II and S6K1 in vascular endothelial inflammation and aging

Yepuri, Gautham ; Velagapudi, Srividya ; Xiong, Yuyan ; Rajapakse, Angana G. ; Montani, Jean-Pierre ; Ming, Xiu-Fen ; Yang, Zhihong

In: Aging Cell, 2012, p. -

Augmented activities of both arginase and S6K1 are involved in endothelial dysfunction in aging. This study was to investigate whether or not there is a crosstalk between arginase and S6K1 in endothelial inflammation and aging in senescent human umbilical vein endothelial cells and in aging mouse models. We show increased arginase-II (Arg-II) expression/activity in senescent endothelial cells....

Université de Fribourg

Arginase iI promotes macrophage inflammatory responses through mitochondrial reactive oxygen species, contributing to insulin resistance and atherogenesis

Ming, Xiu‐Fen ; Rajapakse, Angana G. ; Yepuri, Gautham ; Xiong, Yuyan ; Carvas, João M. ; Ruffieux, Jean ; Scerri, Isabelle ; Wu, Zongsong ; Popp, Katja ; Li, Jianhui ; Sartori, Claudio ; Scherrer, Urs ; Kwak, Brenda R. ; Montani, Jean‐Pierre ; Yang, Zhihong

In: Journal of the American Heart Association, 2012, p. -

Background Macrophage‐mediated chronic inflammation is mechanistically linked to insulin resistance and atherosclerosis. Although arginase I is considered antiinflammatory, the role of arginase II (Arg‐II) in macrophage function remains elusive. This study characterizes the role of Arg‐II in macrophage inflammatory responses and its impact on obesity‐linked type II...