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

mTOR signalling: the molecular interface connecting metabolic stress, aging and cardiovascular diseases

Yang, Zhihong ; Ming, Xiu-Fen

In: Obesity Reviews, 2012, vol. 13, no. S2, p. 58–68

The continuing increase in the prevalence of obesity and metabolic disorders such as type-II diabetes and an accelerating aging population globally will remain the major contributors to cardiovascular mortality and morbidity in the 21st century. It is well known that aging is highly associated with metabolic and cardiovascular diseases. Growing evidence also shows that obesity and metabolic...

Université de Fribourg

Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in aging: inhibition by resveratrol

Rajapakse, Angana Gupta ; Yepuri, Gautham ; Carvas, João M. ; Stein, Sokrates ; Matter, Christian M. ; Scerri, Isabelle ; Ruffieux, Jean ; Montani, Jean-Pierre ; Ming, Xiu-Fen ; Yang, Zhihong

In: PLoS ONE, 2011, vol. 6, no. 4, p. e19237

Mammalian target of rapamycin (mTOR)/S6K1 signalling emerges as a critical regulator of aging. Yet, a role of mTOR/S6K1 in aging-associated vascular endothelial dysfunction remains unknown. In this study, we investigated the role of S6K1 in aging-associated endothelial dysfunction and effects of the polyphenol resveratrol on S6K1 in aging endothelial cells. We show here that senescent endothelial...

Université de Fribourg

Opposing and uncoupling effects of mTOR and S6K1 in the regulation of endothelial tissue factor expression

Ming, Xiu-Fen ; Rajapakse, Angana Gupta ; Carvas, João Miguel ; Ruffieux, Jean ; Yang, Zhihong

In: Febs Letters, 2010, vol. 58, no. 1, p. 135-140

Rapamycin has been reported to enhance tissue factor (TF) expression. The present study investigated roles of mammalian target of rapamycin (mTOR) and its downstream S6K1 in this process. We showed here that, consistent with rapamycin, knocking-down mTOR enhanced thrombin-induced TF mRNA and protein levels, whereas silencing S6K1 mitigated up-regulation of TF protein but not TF mRNA level. The...

Université de Fribourg

Sirolimus increases tissue factor expression but not activity in cultured human vascular smooth muscle cells

Zhu, Shengsi ; Viswambharan, Hema ; Gajanayake, Thusitha ; Ming, Xiu-Fen ; Yang, Zhihong

In: BMC Cardiovascular Disorders, 2007, vol. 5, p. 22

Background Sirolimus-eluting stents (CYPHER stents) demonstrated remarkable efficacy in reducing restenosis rates in patients with coronary artery disease. There is a concern of sub-acute and late stent thrombosis. Tissue factor (TF) is critical in thrombosis. This study investigated the effect of sirolimus on TF expression and activity in cultured human vascular smooth muscle cells...

Université de Fribourg

Thrombin Stimulates Human Endothelial Arginase Enzymatic Activity via RhoA/ROCK Pathway

Ming, Xiu-Fen ; Barandier, Christine ; Viswambharan, Hema ; Kwak, Brenda R. ; Mach, François ; Mazzolai, Lucia ; Hayoz, Daniel ; Ruffieux, Jean ; Rusconi, Sandro ; Montani, Jean-Pierre ; Yang, Zhihong

In: Circulation, 2004, vol. 110, p. 3708-3714

Background— Arginase competes with endothelial nitric oxide synthase (eNOS) for the substrate L-arginine and decreases NO production. This study investigated regulatory mechanisms of arginase activity in endothelial cells and its role in atherosclerosis. Methods and Results— In human endothelial cells isolated from umbilical veins, thrombin concentration- and time-dependently stimulated...