A5077806459- Cardiac Ischemia and Reperfusion
- Nitric Oxide and Endothelin Effects
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Redox biology and oxidative stress
- Heavy Metal Exposure and Toxicity
- Mitochondrial Function and Pathology
- Arsenic contamination and mitigation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Signaling Pathways in Disease
- Cardiac Fibrosis and Remodeling
- Cardiac Arrest and Resuscitation
- MicroRNA in disease regulation
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- Cancer-related molecular mechanisms research
- ATP Synthase and ATPases Research
- Renin-Angiotensin System Studies
- Caveolin-1 and cellular processes
- Adipose Tissue and Metabolism
- Heart Failure Treatment and Management
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Eicosanoids and Hypertension Pharmacology
Johns Hopkins University
2016-2025
Johns Hopkins Medicine
2011-2024
Bloomberg (United States)
2016-2023
Tongji Hospital
2017
Huazhong University of Science and Technology
2017
Vanderbilt University Medical Center
2017
National Heart Lung and Blood Institute
2010-2015
National Institutes of Health
2011-2015
Center for Systems Biology
2011-2014
Johns Hopkins Bayview Medical Center
2011
The mitochondrial permeability transition pore (mPTP) opening plays a critical role in mediating cell death during ischemia/reperfusion (I/R) injury. Our previous studies have shown that cysteine 203 of cyclophilin D (CypD), mPTP mediator, undergoes protein S-nitrosylation (SNO). To investigate the activation, we mutated CypD to serine residue (C203S) and determined its effect on opening. Treatment WT mouse embryonic fibroblasts (MEFs) with H(2)O(2) resulted an 50% loss calcein fluorescence,...
Redox modifications play an important role in many cellular processes, including cell death. Ischemic preconditioning (IPC) has been shown to involve redox signaling. Protein S-nitrosylation (SNO) is increased following myocardial IPC, and SNO thought provide cardioprotection, part, by reducing cysteine oxidation during ischemia/reperfusion (IR) injury. To test the hypothesis that provides shielding against IR We developed a new method measure protein using resin-assisted capture (Ox-RAC),...
S-nitrosylation (SNO) is a reversible protein modification that has the ability to alter activity of target proteins. However, only small number SNO proteins have been found in myocardium, and even fewer specific sites identified. Therefore, this study aims characterize potential myocardium. We utilized modified version SNO-resin-assisted capture technique tandem with mass spectrometry. In brief, biotin switch was performed using perfused mouse heart homogenates incubated or without...
MicroRNA (miRNA) is a type of noncoding RNA that can repress the expression target genes through posttranscriptional regulation. In addition to numerous physiologic roles for miRNAs, they play an important role in pathophysiologic processes affecting cardiovascular health. Previously, we reported nuclear encoded microRNA (miR-181c) present heart mitochondria, and importantly, its overexpression affects mitochondrial function by regulating gene expression.To investigate further how miR-181...
The sarcoplasmic reticulum (SR) Ca(2+) release channel (ryanodine receptor, RyR2) has been proposed to be an end target of neuronal nitric oxide synthase (NOS1) signalling. purpose this study is investigate the mechanism NOS1 modulation RyR2 activity and corresponding effect on myocyte function. Myocytes were isolated from knockout (NOS1(/)) wild-type mice. NOS1(/) myocytes displayed a decreased fractional SR release, also led reduced S-nitrosylation levels. channels hearts had open...
Nitric oxide (NO) and protein S-nitrosylation (SNO) have been shown to play important roles in ischaemic preconditioning (IPC)-induced acute cardioprotection. The majority of proteins that show increased SNO following IPC are localized the mitochondria, our recent studies suggest caveolae transduce NO/SNO cardioprotective signalling hearts. Due close association between subsarcolemmal mitochondria (SSM) sarcolemma/caveolae, we tested hypothesis SSM, rather than interfibrillar (IFM), major...
MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. Here, we show present in blood circulation acts as myokine to facilitate tissue injury-repair and regeneration. Transgenic mice with sustained elevation of bloodstream (tPA-MG53) have healthier longer life-span when compared littermate wild type mice. The tPA-MG53 normal glucose handling insulin signaling skeletal muscle, does not deleterious impact on db/db More importantly, display...
Cardiovascular disease is the leading cause of mortality in US. Studies suggest a role for environmental exposures etiology cardiovascular disease, including exposure to arsenic through drinking water. Arsenic during pregnancy has been shown have effects on offspring, but few studies examined impacts maternal health. While our prior work documented detrimental effect heart pregnancy, current study examines gestational postpartum. Timed-pregnant wild-type (C57BL/6J) mice were exposed 0, 100...
Signaling via endothelial nitric oxide synthase (NOS3) limits the heart's response to β-adrenergic (β-AR) stimulation, which may be protective against arrhythmias. However, mechanistic data are limited. Therefore, we performed simultaneous measurements of action potential (AP, using patch clamp), Ca 2+ transients (fluo 4), and myocyte shortening (edge detection). L-type current ( I ) was directly measured by whole cell ruptured patch-clamp technique. Myocytes were isolated from wild-type...
Rationale: S-nitrosylation (SNO) is a reversible, thiol-based protein modification that plays an important role in the myocardium by protecting critical cysteine residues from oxidation. However, little known with regard to percentage of given modified SNO (ie, occupancy). Current methods allow for relative quantification levels, but not determination occupancy. Objective: To develop method measurement occupancy, and apply this methodology determine occupancy myocardium. Methods Results: We...
Abstract Inorganic scale dissolution with hydrochloric acid requires various supplemental chemistries to ensure effective and complete contact of scale. The deployment multiple adds complexity cost remediation jobs. To streamline enhance acidizing efficiency, a biosurfactant-based additive has been developed. This microemulsion, which combines functional chemistry multifunctional biosurfactant molecules, eliminates the need for additional chemicals, serving as solvent, surfactant,...
Studies have shown that neuronal nitric oxide synthase (nNOS, NOS1) knockout mice (NOS1-/-) increased or decreased contractility, but consistently found a slowed rate of intracellular Ca2+ ([Ca2+]i) decline and relengthening. Contraction [Ca2+]i are determined by many factors, one which is phospholamban (PLB). The purpose this study to determine the involvement PLB in NOS1-mediated effects. Force-frequency experiments were performed trabeculae isolated from NOS1-/- wild-type (WT) mice. We...
Aims: Nitric oxide (NO) and protein S-nitrosylation (SNO) play important roles in ischemic preconditioning (IPC)-induced cardioprotection. Mitochondria are key regulators of preconditioning, most proteins showing an increase SNO with IPC mitochondrial. The aim this study was to address how transduces NO/SNO signaling mitochondria the heart. Results: In using Langendorff perfused mouse hearts, we found that IPC-induced cardioprotection blocked by treatment either N-nitro-L-arginine methyl...
Previous studies have shown a role for nitric oxide and S-nitrosylation (SNO) in postconditioning (PostC), but specific SNO proteins sites not been identified the myocardium after PostC. In this study, we examined signaling PostC using Langendorff-perfused mouse heart model. After 20 min of equilibrium perfusion 25 global ischemia, was applied at beginning reperfusion with six cycles 10 s ischemia. The total period 90 min. Compared ischemia-reperfusion (I/R) control, significantly reduced...
Mitochondrial proteins have been shown to be common targets of S-nitrosylation (SNO), but the existence a mitochondrial source nitric oxide remains controversial. SNO is oxide-dependent thiol modification that can regulate protein function. Interestingly, trans-S-nitrosylation represents potential pathway for import into mitochondria. The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which has act as nuclear trans-S-nitrosylase, also enter However, function GAPDH in...
Protein S-nitros(yl)ation (SNO) has been implicated as an essential mediator of nitric oxide-dependent cardioprotection. Compared with males, female hearts exhibit higher baseline levels protein SNO and associated this, reduced susceptibility to myocardial ischemia-reperfusion injury. Female also enhanced S-nitrosoglutathione reductase (GSNO-R) activity, which would typically favor decreased GSNO-R mediates catabolism. Because levels, we hypothesized that is component sex-dependent...