A5037134872- Amyotrophic Lateral Sclerosis Research
- Nitric Oxide and Endothelin Effects
- Heat shock proteins research
- Cardiac pacing and defibrillation studies
- Nerve injury and regeneration
- Neurogenetic and Muscular Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiac Arrhythmias and Treatments
- Mitochondrial Function and Pathology
- Reproductive Physiology in Livestock
- Cardiac Imaging and Diagnostics
- Spinal Cord Injury Research
- Cardiac electrophysiology and arrhythmias
- Redox biology and oxidative stress
- Cancer, Hypoxia, and Metabolism
- Biochemical effects in animals
- Neuroscience of respiration and sleep
- Alzheimer's disease research and treatments
- Infective Endocarditis Diagnosis and Management
- Reproductive System and Pregnancy
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Acute Myocardial Infarction Research
- Cardiovascular Function and Risk Factors
- Neurogenesis and neuroplasticity mechanisms
Oregon State University
2019-2024
Florida International University
2024
Hospital Universitario Infanta Leonor
2017-2024
Universidad Complutense de Madrid
2019-2024
Hospital General Universitario Gregorio Marañón
2005-2024
University of Alabama at Birmingham
1998-2022
University of Central Florida
2011-2017
Xiaomi (China)
2015
Ross School
2015
Universidad del Valle de Guatemala
2010-2013
Primary cultures of rat embryonic motor neurons deprived brain-derived neurotrophic factor (BDNF) induce neuronal nitric oxide synthase (NOS) within 18 hr. Subsequently, >60% the undergo apoptosis between and 24 hr after plating. Nitro-L-arginine nitro-L-arginine methyl ester (L-NAME) prevented neuron death induced by trophic deprivation. Exogenous generation at concentrations lower than 100 nM overcame protection L-NAME. Manganese tetrakis (4-benzoyl acid) porphyrin, a cell-permeant...
Abstract: Peroxynitrite is a powerful oxidant formed by the near‐diffusion‐limited reaction of nitric oxide with superoxide. Large doses peroxynitrite (>2 m M ) resulted in rapid cell swelling and necrosis undifferentiated PC12 cells. However, brief exposure to lower concentrations (EC 50 = 850 µ initially (3–4 h) caused minimal damage low‐density cultures. By 8 h, cytoplasmic shrinkage nuclear condensation fragmentation became increasingly evident. After 24 36% peroxynitrite‐treated...
NO 2 Tyr (3-Nitrotyrosine) is a modified amino acid that formed by nitric oxide-derived species and has been implicated in the pathology of diverse human diseases. Nitration active-site tyrosine residues known to compromise protein structure function. Although free produced abundant concentrations under pathological conditions, its capacity alter function at translational or posttranslational level unknown. Here, we report transported into mammalian cells selectively incorporated extreme...
Concentrations of up to 1.5 milliunits/ml xanthine oxidase (XO) (1.1 μg/ml) are found circulating in plasma during diverse inflammatory events. The saturable, high affinity binding extracellular XO vascular endothelium and the effects cell on both catalytic activity differentiated function reported herein. Xanthine purified from bovine cream bound specifically with (K d = 6 nm) at 4 °C aortic endothelial cells, increasing specific 10-fold. oxidase-cell was not inhibited by serum or albumin...
Abstract Reactive astrocytes frequently surround degenerating motor neurons in patients and transgenic animal models of amyotrophic lateral sclerosis (ALS). We report here that reactive the ventral spinal cord ALS‐mutant G93A superoxide dismutase (SOD) mice expressed nerve growth factor (NGF) regions where p75 neurotrophin receptor (p75 NTR ) were immunoreactive for nitrotyrosine. Cultured incubated with lipopolysaccharide (LPS) or peroxynitrite became accumulated NGF culture medium. caused...
Over-expression of mutant copper, zinc superoxide dismutase (SOD) in mice induces ALS and has become the most widely used model neurodegeneration. However, no pharmaceutical agent 20 years extended lifespan by more than a few weeks. The Copper-Chaperone-for-SOD (CCS) protein completes maturation SOD inserting but paradoxically human CCS causes co-expressing to die within two weeks birth. Hypothesizing that co-expression created copper deficiency spinal cord, we treated these pups with...
Mutations in Cu,Zn superoxide dismutase (SOD1) cause familial amyotrophic lateral sclerosis (FALS), a rapidly fatal motor neuron disease. Mutant SOD1 has pleiotropic toxic effects on neurons, among which mitochondrial dysfunction been proposed as one of the contributing factors demise. Mitochondria are highly dynamic neurons; they constantly reshaped by fusion and move along neurites to localize at sites high-energy utilization, such synapses. The finding abnormal mitochondria accumulation...
Oxidative stress is a widely recognized cause of cell death associated with neurodegeneration, inflammation, and aging. Tyrosine nitration in these conditions has been reported extensively, but whether tyrosine marker or plays role the cell-death processes was unknown. Here, we show that single residue on small proportion 90-kDa heat-shock protein (Hsp90), sufficient to induce motor neuron by P2X7 receptor-dependent activation Fas pathway. Nitrotyrosine at position 33 56 stimulates toxic...
Abstract Oxidative stress mediated by nitric oxide (NO) and its toxic metabolite peroxynitrite has previously been associated with motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Degenerating spinal neurons familial sporadic ALS are typically surrounded reactive astrocytes expressing the inducible form of NO synthase (iNOS), suggesting that astroglia may have a pathogenic role ALS. We report here brief exposure cord astrocyte monolayers to (0.25–1 mM) provoked long‐lasting...
Trophic factor deprivation induces neuronal nitric oxide synthase (NOS) and apoptosis of rat embryonic motor neurons in culture. We report here that constitutively express endothelial NOS helps support the survival cultured with brain-derived neurotrophic (BDNF) by activating oxide-dependent soluble guanylate cyclase. Exposure BDNF-treated to nitro- l -arginine methyl ester ( -NAME) decreased cell 40–50% 24 hr after plating. Both low steady-state concentrations exogenous (<0.1 μ m ) cGMP...
Abstract Fibroblast growth factor‐1 (FGF1 or acidic FGF) is highly expressed in motor neurons. FGF‐1 released from cells by oxidative stress, which might occur SOD‐1 aberrant function amyotrophic lateral sclerosis (ALS). Although known to be neuroprotective after spinal cord injury axotomy, we found that could activate astrocytes a manner decreased neuron survival co‐cultures. induced accumulation of the FGF receptor 1 (FGFR1) astrocyte nuclei and potently stimulated nerve factor (NGF)...
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease, protein aggregation has been proposed as possible pathogenetic mechanism. However, the aggregate constituents are poorly characterized so knowledge on role of in pathogenesis limited.We carried out proteomic analysis composition insoluble fraction, model aggregates, from familial ALS (fALS) mouse at different disease stages. We identified several proteins enriched detergent-insoluble fraction already...
Ventilator strategies allowing for increases in carbon dioxide (CO 2 ) tensions (hypercapnia) are being emphasized to ameliorate the consequences of inflammatory-mediated lung injury. Inflammatory responses lead generation reactive species including superoxide (O − ), nitric oxide (·NO), and their product peroxynitrite (ONOO ). The reaction CO ONOO can yield nitrosoperoxocarbonate adduct ONOOCO , a more potent nitrating than . Based on these premises, monolayers fetal rat alveolar epithelial...
Recent data suggest that either excessive or deficient levels of protein S-nitrosylation may contribute to disease. Disruption S -nitrosothiol (SNO) homeostasis result not only from altered nitric oxide (NO) synthase activity but also alterations in the denitrosylases remove NO groups. A subset patients with familial amyotrophic lateral sclerosis (ALS) have mutations superoxide dismutase 1 (SOD1) increase denitrosylase SOD1. Here, we show increased SOD1 mutants leads an aberrant decrease...
Vascular endothelial growth factor (VEGF) plays a neuroprotective role in mice harboring mutations of copper–zinc superoxide dismutase 1 (SOD1) familial amyotrophic lateral sclerosis (ALS). Conversely, the loss VEGF expression through genetic depletion can give rise to phenotype resembling ALS independent SOD1 mutations. Here, we observe profound downregulation mRNA spinal cords G93A that occurred early course disease. Using an vitro culture model glial cells expressing mutant SOD1,...