Zhengbing ZhugeKarolinska Institutet | KI · Department of Physiology and Pharmacology
Zhengbing Zhuge
Doctor of Philosophy
About
40
Publications
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452
Citations
Citations since 2017
Introduction
Interested in cardiovascular and kidney diseases, good at using various technologies to study vessel functions.
Skills and Expertise
Publications
Publications (40)
Despite wide appreciation of the biological role of nitric oxide (NO) synthase (NOS) signaling, questions remain about the chemical nature of NOS-derived bioactivity. Here we show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species which can exchange proteins, partition to the hydrophobic phase, and directly activa...
Background & aims
Nitric oxide bioactivity (NO) from endothelial NO synthase (eNOS) importantly contributes to the maintenance of vascular homeostasis, and reduced eNOS activity has been associated with cardiovascular disease. Emerging evidence suggest interaction(s) between red blood cells (RBCs) and the endothelium in vascular control; however, t...
Arginase 1 (Arg1) is a ubiquitous enzyme belonging to the urea cycle that catalyzes the conversion of l-arginine into l-ornithine and urea. In endothelial cells (ECs), Arg1 was proposed to limit the availability of l-arginine for the endothelial nitric oxide synthase (eNOS) and thereby reduce nitric oxide (NO) production, thus promoting endothelial...
Background
Renal fibrosis, associated with oxidative stress and nitric oxide (NO) deficiency, contributes to the development of chronic kidney disease and renal failure. As major energy source in maintaining renal physiological functions, tubular epithelial cells with decreased fatty acid oxidation play a key role in renal fibrosis development. Ino...
Organic nitrates are widely used to restore endogenous nitric oxide (NO) levels reduced by endothelial nitric oxide synthase dysfunction. However, these drugs are associated with undesirable side effects, including tolerance. This study aims to investigate the cardiovascular effects of the new organic nitrate 1,3-diisobutoxypropan-2-yl nitrate (NDI...
Vasodilation is a cornerstone of inflammation physiology. By regulating vasodilation and tissue entry of T cells, CD4+ T lymphocytes expressing choline acetyltransferase (ChAT), a key enzyme for biosynthesis of the vasorelaxant acetylcholine (ACh), critically link immunity with vascular biology in mice. However, the characterization of primary huma...
Rationale:
Pre-eclampsia is a multisystem disorder associated with systemic vascular dysfunction and decreased nitric oxide (NO) bioactivity. Arginase competes with NO synthase (NOS) for L-arginine, and its upregulation may reduce NOS-derived NO formation or induce production of reactive oxygen species (ROS) via uncoupling of NOS, resulting in end...
Background:
Renal ischemia-reperfusion (IR) injury is a common cause of acute kidney injury (AKI), which is associated with oxidative stress and reduced nitric oxide (NO) bioactivity and increased risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD). New strategies that restore redox balance may have therapeutic implica...
Background/purpose:
Unhealthy dietary habits contribute to the increasing incidence of metabolic syndrome and type 2 diabetes (T2D), which is accompanied by oxidative stress, compromised nitric oxide (NO) bioavailability and increased cardiovascular risk. Apart from lifestyle changes, biguanides such as metformin are the first-line pharmacological...
Emerging evidence indicates that dietary nitrate can reverse several features of the metabolic syndrome, but the underlying molecular mechanisms still remain elusive. The aim of the present study was to explore mechanisms involved in the effects of dietary nitrate on the metabolic dysfunctions induced by high-fat diet (HFD) in mice. Four weeks old...
Nitric oxide (NO) is a key signalling molecule in the regulation of cardiometabolic function and impaired bioactivity is considered to play an important role in the onset and progression of cardiovascular and metabolic disease. Research has revealed an alternative NO-generating pathway, independent of NO synthase (NOS), in which the inorganic anion...
Aims:
Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is suggested to increase the risk for cardiovascular disease. How PCOS may lead to adverse cardiac outcomes is unclear and here we hypothesized that prenatal exposure to dihydrotestosterone (DHT) and/or maternal obesity in mice induce adverse metabolic and cardiac programming i...
BACKGROUND:
Nitrosation of a conserved cysteine residue at position 93 in the hemoglobin β chain (β93C) to form S-nitroso (SNO) hemoglobin (Hb) is claimed to be essential for export of nitric oxide (NO) bioactivity by the red blood cell (RBC) to mediate hypoxic vasodilation and cardioprotection.
METHODS:
To test this hypothesis, we used RBCs from...
Polycystic ovary syndrome (PCOS) is suggested to increase the risk for cardiovascular disease and type 2 diabetes. We hypothesized here that prenatal exposure to dihydrotestosterone (DHT) and/or maternal obesity lead to adverse metabolic and cardiac programming in the female offspring. The maternal obese PCOS phenotype was induced in mice by prenat...
Several experimental and clinical studies have shown that dietary nitrate supplementation can increase nitric oxide bioavailability. In the oral cavity, commensal bacteria reduce nitrate to nitrite, which is subsequently absorbed into the circulation where reduction to nitric oxide by enzymatic systems occur. Although it is well-known that boosting...
For more details:
https://www.pnas.org/content/116/1.cover-expansion
Significance
Liver steatosis, or fatty liver, is the most common liver disease in the world, affecting up to 25% of all Americans. There is currently no approved drug available for this condition, which may progress to serious disease, including steatohepatitis, fibrosis, and cirrhosis. Here, we show in rodent and human models of metabolic syndrome...
Background/aims:
Canonical Wnt signaling is involved in oxidative stress, vasculopathy and diabetes mellitus but its role in diabetic renal microvascular dysfunction is unclear. We tested the hypothesis that enhanced canonical Wnt signaling in renal afferent arterioles from diabetic mice increases reactive oxygen species (ROS) and contractions to...
Rationale:
Development and progression of cardiovascular diseases, including hypertension, are often associated with impaired nitric oxide synthase (NOS) function and nitric oxide (NO) deficiency. Current treatment strategies to restore NO bioavailability with organic nitrates are hampered by undesirable side effects and development of tolerance....
Supplementary material
Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exer...
Aim:
Afferent arterioles (AA) hold a key position in the regulation of renal blood flow and glomerular filtration rate. Being the effector site of tubuloglomerular feedback the afferent arteriole contributes to the renal handling of sodium and fluid. Dehydration goes along with increased renal interstitial protein concentration. Here, the hypothes...
Supplementary material
Ischemia-reperfusion (IR) injury involves complex pathological processes in which reduction of nitric oxide (NO) bioavailability is suggested as a key factor. Inorganic nitrate can form NO in vivo via NO synthase-independent pathways and may thus provide beneficial effects during IR. Herein we evaluated the effects of dietary nitrate supplementatio...
In this report, we describe the synthesis and characterization of 1,3-bis(hexyloxy)propan-2-yl nitrate (NDHP), a novel organic mono nitrate. Using purified xanthine oxidoreductase (XOR), chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy, we found that XOR catalyzes nitric oxide (NO) generation from NDHP under anaerobic condit...
Inorganic nitrate and nitrite from dietary and endogenous sources are metabolized to nitric oxide (NO) and other bioactive nitrogen oxides that affect blood pressure. The mechanisms for nitrite bioactivation are unclear but recent studies in rodents suggest that gastric acidity may influence the systemic effects of this anion. In a randomized doubl...
Inorganic nitrate and nitrite from dietary and endogenous sources are metabolized to NO and other bioactive nitrogen oxides that affect blood pressure. The mechanisms for nitrite bioactivation are unclear, but recent studies in rodents suggest that gastric acidity may influence the systemic effects of this anion. In a randomized, double-blind, plac...
Figure S1. Western blot membranes. Less cropped images of all Western blot membranes for the kidney (A) and BMDMs (B, C) are presented together with the molecular weight (MW) of each protein and the MW size marker. For BMDMs (B, C), membranes were cut after the transfer step according to MW of target proteins to enable detection of different protei...
Background
Early‐life reduction in nephron number (uninephrectomy [UNX]) and chronic high salt (HS) intake increase the risk of hypertension and chronic kidney disease. Adenosine signaling via its different receptors has been implicated in modulating renal, cardiovascular, and metabolic functions as well as inflammatory processes; however, the spec...
Maidong, known as Ophiopogon japonicus, is one of the two basic ingredients of Shenmai injection, which is a widely used herbal preparation in traditional Chinese medicine (TCM) for the treatment of atherosclerotic coronary heart disease and viral myocarditis. Previously, the ethanol extract of Maidong activated the pregnane X receptor (PXR) signal...
To investigate the inhibitory effects of hydroxysafflor yellow A (HSYA) on the protein glycation in vitro. Using BSA-glucose assay, BSA-methylglyoxal (MGO) assay, and N-acetylglycyl-lysine methyl ester (G.K.) peptide-ribose assay, inhibitory effects of HSYA were investigated. Advanced glycation endproducts (AGEs) production was assessed by AGEs-spe...
Projects
Project (1)
PURPOSE AND AIMS
This translational project aims to explore and further characterize the novel concept that the balance between NADPH oxidase (NOX)-derived superoxide (O2-) and nitric oxide (NO) signaling in the microvasculature plays a key role in the triad of renal, cardiovascular and metabolic disorders. State of the art techniques are used to unravel the mechanisms and to investigate therapeutic value of:
A) Stimulating the nitrate (NO3)-nitrite (NO2)-NO pathway
B) Modulating adenosine A1, A2, A3 receptor signaling
A) STIMULATING THE NO3 - NO2 - NO PATHWAY
This project investigates the underlying mechanism(s) and the therapeutic value associated with nitrate and nitrite supplementation in renal, cardiovascular and metabolic disorders.
B) MODULATING ADENOSINE A1, A2, A3 RECEPTOR SIGNALING
This project investigates the therapeutic value and the underlying mechanism(s) of inhibiting adenosine A1 or A3 or stimulating A2 receptors in renal, cardiovascular and metabolic disorders.
