- Nitric Oxide and Endothelin Effects
- Pluripotent Stem Cells Research
- Adipokines, Inflammation, and Metabolic Diseases
- DNA Repair Mechanisms
- Lipid metabolism and disorders
- CRISPR and Genetic Engineering
- Heat shock proteins research
- Erythrocyte Function and Pathophysiology
- Venous Thromboembolism Diagnosis and Management
- Synthesis and Biological Evaluation
- Phosphodiesterase function and regulation
- Cardiovascular Disease and Adiposity
- Renin-Angiotensin System Studies
- Eicosanoids and Hypertension Pharmacology
- Phenothiazines and Benzothiazines Synthesis and Activities
- Hemoglobin structure and function
- Cell Adhesion Molecules Research
- Cardiovascular Health and Disease Prevention
- Bioactive Compounds and Antitumor Agents
- Cancer, Stress, Anesthesia, and Immune Response
- Ion channel regulation and function
- Protein Kinase Regulation and GTPase Signaling
- Synthesis and Catalytic Reactions
- Receptor Mechanisms and Signaling
- Cancer Mechanisms and Therapy
VA Palo Alto Health Care System
2023-2024
George Washington University
2011-2022
Research Institute of Therapy and Preventive Medicine
2022
National Research Center for Preventive Medicine
2022
Sechenov University
2018-2020
Institute of Molecular Medicine
2008-2011
Brown Foundation
2008-2011
The University of Texas Health Science Center at Houston
2005-2011
Washington University Medical Center
2011
The University of Texas MD Anderson Cancer Center
2011
Nitric oxide (NO) is involved in number of physiological and pathological events. Our previous studies demonstrated a differential expression NO signaling components mouse human ES cells. Here, we demonstrate the effect donors soluble guanylyl cyclase (sGC) activators differentiation cells into myocardial results with an increase Nkx2.5 myosin light chain (MLC2) mRNA on exposure to decrease both cardiac-specific genes nonspecific NOS inhibitor concomitant levels sGC α 1 subunit. Although...
In human erythrocyte membranes incubated with [adenylate-32P]NAD the 36 kDa protein is predominantly labeled. The labeling greatly stimulated by nitroprusside in presence of dithiothreitol. We have purified and identified this modification as cysteine-specific mono(ADP-ribosylation) because: (i) occurred only when [32P]NAD was replaced adenine[U-14C]NAD, but not [carbonyl-14C]NAD; (ii) treatment prelabeled snake venom phosphodiesterase led to releasing 5'-[32P]AMP; (iii) bond between...
This report demonstrates that incubation of cytotoxic T cells with NAD causes suppression their ability to proliferate in response stimulator or lyse targets. Effects are evident after for 3 h concentrations as low 1 microM and sustained many hours removal from culture media. Suppression is a result the failure CTL form specific conjugates targets well lower level activation TCR-mediated stimulation, although transmembrane signaling demonstrable. Metabolites such nicotinamide, ADP-ribose,...
Acute secretory diarrhea induced by infection with enterotoxigenic strains of Escherichia coli involves binding stable toxin (STa) to its receptor on the intestinal brush border, guanylyl cyclase type C (GC-C). Intracellular cGMP is elevated, inducing increase in chloride efflux and subsequent accumulation fluid lumen. We have screened a library compounds identified pyridopyrimidine derivatives {5-(3-bromophenyl)-1,3-dimethyl-5,11-dihydro-1 H -indeno[2′,1′:5,6]pyrido[2,3- d...
The nitric oxide (NO)-cyclic GMP pathway contributes to human stem cell differentiation, but NO free radical production can also damage DNA, necessitating a robust DNA response (DDR) ensure survival. How the DDR is affected by differentiation unclear. Differentiation of cells, either inducible pluripotent or embryonic derived, increased residual as determined γ-H2AX and 53BP1 foci, with S-phase-specific chromosomal aberration after exposure DNA-damaging agents, suggesting reduced homologous...
Heterodimeric αβ soluble guanylyl cyclase (sGC) is a recognized receptor for nitric oxide (NO) and mediates many of its physiological functions. Although it has been clear that the heme moiety coordinated by His-105 β subunit crucial mediating activation enzyme NO, not understood whether plays any role in function absence NO. Here we analyze effects biochemical genetic removal reconstitution on activity enzyme. Detergent-induced loss from wild-type resulted several-fold This was inhibited...
The NO and cGMP signaling pathways are of broad physiological pathological significance. We compared the NO/soluble guanylyl cyclase (sGC)/cGMP pathway in human glioma tissues cell lines with that healthy control samples demonstrated sGC expression is significantly lower preparations. Our analysis GEO databases (National Cancer Institute) further revealed a statistically significant reduction transcript levels specimens. On other hand, particulate (membrane) cyclases (pGC) cGMP-specific...
Abstract Objective PBR characterizes penetration of red blood cells inside glycocalyx and its thickness can have profound impact on microcirculation other vascular parameters. The goal our study was to reliably quantify assess potential use as a new marker cardiovascular pathology. Methods included 208 patients (123 men 85 women from 40 65 years age) with various grades SCORE risk index IHD. quantified by sidestream dark field capillaroscopy green light excitation. Cutaneous evaluated laser...
Nitric oxide (NO) is an important functional regulator that contributes to progression of various cardiovascular diseases. We studied associations between nitric metabolites, nitrite and nitrate (NOx), mortality in a prospective 3-year follow-up cohort study 1,869 elderly patients aged over 55 years. The Cox proportional hazard regression model was adjusted for multiple factors including sex, age, risk corresponding preexisting conditions, serum inflammatory markers (C-reactive protein,...
Certain heterocyclic N‐oxides are vasodilators and inhibitors of platelet aggregation. The pharmacological activity the furoxan derivative condensed with pyridazine di‐N‐oxide 4,7‐dimethyl‐1,2,5‐oxadiazolo[3,4‐ d ]pyridazine 1,5,6‐trioxide (FPTO) corresponding furazan (FPDO) was studied. FPTO reacted thiols generating nitrite (NO), S‐nitrosoglutathione hydroxylamine (nitroxyl) converted oxyHb to metHb. FPDO did not generate detectable amounts NO‐like species but oxyHb. haem‐dependently...
Adiponectin is encoded by the ADIPOQ gene and participates in pathogenesis of cardiovascular metabolic diseases. The goal study was to assess associations rs17300539, rs266729, rs182052, rs2241766, rs17366743 single nucleotide polymorphisms (SNPs) with concentrations serum adiponectin coronary atherosclerosis type 2 diabetes mellitus 447 patients (316 men 131 women) subjected angiography. SNPs participants were genotyped using real-time PCR. Multivariate linear regression adjusted for...
Noninvasive diagnostics of early stages coronary artery disease and discrimination between various extents vascular lesions in patients is an important clinical problem especially considering wide spread use cholesterol lowering drugs that affect lipid lipoprotein profiling. The main goal our study was to evaluate applicability new combinations noninvasive biomarkers such as leptin insulin adiponectin endothelin ratios, for detection atherosclerosis versus later the disease.A number...
Abstract Background Nitric oxide (NO) is one of the key regulators vascular function. Abnormal NO signalling linked to various cardiovascular diseases. We studied associations between circulating levels metabolites, nitrite and nitrate (NOx) total mortality in a prospective 8‐year follow‐up cohort study 1869 patients aged over 55 years. Materials methods The Cox proportional hazard ratio (HR) regression models were adjusted for multiple risk‐related variables. Post hoc Kaplan‐Meier survival...
Soluble guanylate cyclase (sGC) is a heterodimer composed of and b subunits. The loss sGCβ1 has been implicated in several vascular nonvascular diseases. Our analysis showed that higher levels breast cancer tissues are correlated with greater survival probability than lower levels. However, there no information on sGC regulation by epigenetic mechanisms. We examined the role histone deacetylase (HDAC) inhibitors regulating sGCα1and -β1 expression human MDA-MB-231 MDA-MB-468 cell lines. class...
Nitric oxide (NO), an important mediator molecule in mammalian physiology, initiates a number of signaling mechanisms by activating the enzyme soluble guanylyl cyclase (sGC). Recently, new role for NO/cyclic guanosine monophosphate embryonic development and cell differentiation has emerged. The changes expression NO synthase isoforms various sGC subunits been demonstrated during human mouse stem (ES) cells differentiation. Previously, our laboratory that nascent α1 transcript undergoes...
Nitric oxide and its metabolites, nitrate nitrite, are important regulators linked to various diseases. We studied the association of fasting serum concentrations combined as NOx, without special diet, with prevalence chronic diseases.Fasting NOx were assayed in a cohort 1087 patients recruited Stress Aging Health Russia study that represents male female population Moscow, Russia, over 55 years age. Chronic diseases recorded based on anamnesis additional assays run characterize immune status...