Xun Zhang

Xun Zhang
University of Strathclyde · Strathclyde Institute of Pharmacy and Biomedical Sciences

PhD

About

32
Publications
15,040
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300
Citations

Publications

Publications (32)
Article
Full-text available
Significance The endothelium is the single layer of cells lining all blood vessels and acts as a central control hub to regulate multiple cardiovascular functions in response to hundreds of physiological stimuli. The detection of various physiological stimuli is distributed in spatially separated sites across the endothelium. Distributed sensing is...
Article
Protease activated receptors (PARs), a subfamily of G-protein-coupled receptors, are activated by cleavage of its extracellular domains. Four mammalian PAR members have been identified (PAR1-4). PAR1 is the thrombin receptor, while PAR2 is activated physiologically by peptides or N-terminal proteolytic cleavage. The resulting cleaved N-termini acts...
Article
The endothelium is the innermost layer of all blood vessels and it controls a host of cardiovascular functions including vascular contractility, hemostasis, inflammation and the exchange of nutrients and waste products between circulating blood and tissue. The importance of the endothelium is clear since changes in the behaviour of this single laye...
Article
Arteries and veins are lined by non-proliferating endothelial cells that play a critical role in regulating blood flow. Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis to fuel each of these energy-demanding processes. However, endothelia...
Article
The endothelium is a sheet of highly-specialised cells that line every blood vessel. Endothelial cells detect, integrate and respond to information from numerous signals, passing this information to neighbouring endothelial cells via intercellular communication to coordinate vascular contractility, inflammation and exchange of products between the...
Article
Full-text available
Background and purpose: Ca2+ influx via TRPV4 triggers Ca2+ release from the IP3 -sensitive internal store to generate repetitive oscillations. While mitochondria are acknowledged regulators of IP3 -mediated Ca2+ release, how TRPV4-mediated Ca2+ signals are regulated by mitochondria is unknown. We show that depolarised mitochondria switch TRPV4 si...
Preprint
Full-text available
Arteries and veins are lined by non-proliferating endothelial cells that play a critical role in regulating blood flow. Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis to fuel each of these energy-demanding processes. However, endothelia...
Conference Paper
Full-text available
Mitochondria are significant regulators of intracellular Ca2+ signalling in the vascular endothelium. Depolarization of the mitochondrial membrane potential (Δψm) inhibits IP3-mediated Ca2+ release and may regulate Ca2+ influx across the plasma membrane. However, precisely how Ca2+ influx is regulated by mitochondria in the endothelium is unknown....
Article
Full-text available
Retinal degeneration, characterized by the progressive death of retinal neurons, is the most common cause of visual impairment. Oxysterols are the cholesterol derivatives produced via enzymatic and/or free radical oxidation that regulate cholesterol homeostasis in the retina. Preclinical and clinical studies have suggested a connection between oxys...
Article
Full-text available
Background and purpose: Coordinated endothelial control of cardiovascular function is proposed to occur by endothelial cell communication via gap junctions and connexins. To study intercellular communication, the pharmacological agents carbenoxolone (CBX) and 18β glycyrrhetinic acid (18βGA) are used widely as connexin inhibitors and gap junction b...
Article
Full-text available
Background Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations that give rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfuncti...
Preprint
Full-text available
Rationale Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations giving rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfunction a...
Article
Full-text available
Hydrogen peroxide (H2O2) is a mitochondrial-derived reactive oxygen species (ROS) that regulates vascular signalling transduction, vasocontraction and vasodilation. Although the physiological role of ROS in endothelial cells is acknowledged, the mechanisms underlying H2O2 regulation of signalling in native, fully-differentiated endothelial cells is...
Article
Full-text available
Endothelial cells line all blood vessels and are critical regulators of vascular tone. In hypertension, disruption of endothelial function alters the release of endothelial-derived vasoactive factors and results in increased vascular tone. Although the release of endothelial-derived vasodilators occurs in a Ca2+-dependent manner, little is known on...
Article
Full-text available
Background and purpose: Transient receptor potential vanilloid 4 (TRPV4) channels are Ca2+ -permeable, nonselective cation channels that mediate large, but highly-localized, Ca2+ signals in the endothelium. The mechanisms that permit highly-localized Ca2+ changes to evoke cell-wide activity are incompletely understood. Here we tested the hypothesi...
Article
Full-text available
The endothelium is the single layer of cells lining all blood vessels, and it is a remarkable cardiovascular control centre. Each endothelial cell has only a small number (on average six) of interconnected neighbours. Yet this arrangement produces a large repertoire of behaviours, capable of controlling numerous cardiovascular functions in a flexib...
Article
Full-text available
Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene are the predominant cause of retinitis pigmentosa. RPGR plays a critical role as a scaffold protein in the regulation of protein trafficking from the basal body to the axoneme, where the cargoes are transported to the outer segments (OSs) of photoreceptors. This trafficking process...
Article
Full-text available
Endothelial cells are reported to be glycolytic and to minimally rely on mitochondria for ATP generation. Rather than providing energy, mitochondria in endothelial cells may act as signaling organelles that control cytosolic Ca2+ signaling or modify reactive oxygen species (ROS). To control Ca2+ signaling, these organelles are often observed close...
Article
Full-text available
Ciliopathies are a group of genetically heterogeneous disorders, characterized by defects in cilia genesis or maintenance. Mutations in the RPGR gene and its interacting partners, RPGRIP1 and RPGRIP1L, cause ciliopathies, but the function of their proteins remains unclear. Here we show that knockdown (KD) of RPGR, RPGRIP1 or RPGRIP1L in hTERT-RPE1...
Article
Full-text available
Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we descr...
Article
Full-text available
Background: Coenzyme Q10 (CoQ10) plays a critical role in mitochondrial oxidative phosphorylation by serving as an electron carrier in the respiratory electron transport chain. CoQ10 also functions as a lipid-soluble antioxidant by protecting lipids, proteins and DNA damaged by oxidative stress. CoQ10 deficiency has been associated with a number o...
Conference Paper
Purpose Retinitis Pigmentosa is a class of inherited retinal degeneration that causes progressive vision impairment even blindness. The mutations of Retinitis Pigmentosa GTPase Regulator (RPGR) gene account for up to 20% of RP cases. RPGR protein is highly expressed at the connecting cilium of vertebrates’ photoreceptors. RPGR protein has the funct...
Article
Full-text available
Photoreceptors are highly specialized sensory neurons that possess a modified primary cilium called the outer segment. Photoreceptor outer segment formation and maintenance require highly active protein transport via a process known as intraflagellar transport. Anterograde transport in outer segments is powered by the heterotrimeric kinesin II and...
Article
Full-text available
Ciliopathies encompass a group of genetic disorders characterized by defects in the formation, maintenance, or function of cilia. Retinitis pigmentosa (RP) is frequently one of the clinical features presented in diverse ciliopathies. RP is a heterogeneous group of inherited retinal disorders, characterized by the death of photoreceptors and affecti...

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