1,721,010 research outputs found
Immobilized purinergic receptor liquid stationary phases for on-line liquid chromatographic determination of drug-receptor affinities
No full textDevelopment of immobilized GPR17-receptor liquid chromatography stationary phase for chromatographic binding studies
No full textDevelopment of immobilized purinergic-receptor liquid stationary phases for on-line screening of potential drug candidates.
No full textPlasma Biomarkers of Poor Muscle Quality in Older Men and Women from the Baltimore Longitudinal Study of Aging
No full textAging is characterized by progressive decline in muscle mass, strength, and quality all of which contribute to functional impairment, falls, mobility disability, and frailty. Circulating factors may provide clues on the mechanisms for decline in muscle quality with aging. Characterizing the metabolic profile associated with reduced muscle quality in older persons could have important translational implications for the early identification of subjects at high risk of developing sarcopenia and the identification of targets for new preventive strategies and treatments. In a pilot cross-sectional, case-control study nested in the Baltimore Longitudinal Study on Aging, we compared circulating metabolites between 79 participants with low muscle quality ratio and 79 controls with high muscle quality, matched by age, sex, and height. The concentrations of 180 metabolites were determined by LC MS/MS, using the Biocrates p180 system, a targeted metabolomics approach. Participants with low muscle quality had significantly higher levels of leucine, isoleucine, tryptophan, serotonin, and methionine, while those with high muscle quality had significantly lower levels of putrescine and the selected phophatidylcholine (PCs) and lysoPCs. The results of this study open a new road for future investigations aimed at identifying new metabolic pathways involved in the decline of muscle quality with aging
A targeted proteomic assay for the measurement of plasma proteoforms related to human aging phenotypes
No full textCirculating polypeptides and proteins have been implicated in reversing or accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8), GDF11, eotaxin, and oxytocin. These proteoforms, which are defined as the protein products arising from a single gene due to alternative splicing and PTMs, have been challenging to study. Both GDF8 and GDF11 have known antagonists such as follistatin (FST), and WAP, Kazal, immunoglobulin, Kunitz, and NTR domain-containing proteins 1 and 2 (WFIKKN1, WFIKKN2). We developed a novel multiplexed SRM assay using LC-MS/MS to measure five proteins related to GDF8 and GDF11 signaling, and in addition, eotaxin, and oxytocin. Eighteen peptides consisting of 54 transitions were monitored and validated in pooled human plasma. In 24 adults, the mean (SD) concentrations (ng/mL) were as follows: GDF8 propeptide, 11.0 (2.4); GDF8 mature protein, 25.7 (8.0); GDF11 propeptide, 21.3 (10.9); GDF11 mature protein, 16.5 (12.4); FST, 29.8 (7.1); FST cleavage form FST303, 96.4 (69.2); WFIKKN1, 38.3 (8.3); WFIKKN2, 32.2 (10.5); oxytocin, 1.9 (0.9); and eotaxin, 2.3 (0.5). This novel multiplexed SRM assay should facilitate the study of the relationships of these proteoforms with major aging phenotypes
Targeted Metabolomics Shows Low Plasma Lysophosphatidylcholine 18:2 Predicts Greater Decline of Gait Speed in Older Adults: The Baltimore Longitudinal Study of Aging
No full textGait speed is an important measure of lower extremity physical performance in older adults and is predictive of disability and mortality. The biological pathways involved in the decline of lower extremity physical performance are not well understood. We used a targeted metabolomics approach to identify plasma metabolites predictive of change in gait speed over time
Altered Plasma Amino Acids and Lipids Associated With Abnormal Glucose Metabolism and Insulin Resistance in Older Adults
No full textGlucose metabolism becomes progressively impaired with older age. Fasting glucose and insulin resistance are risk factors for premature death and other adverse outcomes. We aimed to identifying plasma metabolites associated with altered glucose metabolism and insulin resistance in older community-dwelling adults
Relationship of Circulating Growth and Differentiation Factors 8 and 11 and Their Antagonists as Measured Using Liquid Chromatography-Tandem Mass Spectrometry With Age and Skeletal Muscle Strength in Healthy Adults
No full textGrowth and differentiation factors 8 (GDF8) and 11 (GDF11) have attracted attention as targets for rejuvenating interventions. The biological activity of these proteins may be affected by circulating antagonists such as their respective prodomains, follistatin (FST315), WFIKKN1, and WFIKKN2. Reports of the relationship of GDF8 and GDF11 and their antagonists with aging and aging phenotypes such as skeletal muscle strength have been conflicting possibly because of difficulties in measuring these proteins and polypeptides
Compounds in Nicotine-free Tobacco Smoke Condensates Bind Allosterically to the α3β4α5 Neuronal Nicotinic Acetylcholine Receptor
No full textv, 35 p.Cigarette smoking is a leading health concern worldwide due to accessibility of cigarettes and the adverse health affects that smoking has on the body. Several of the health risks associated with cigarette smoking are due to the addictive properties of nicotine. Nicotine affects the body by binding to neuronal nicotinic acetylcholine receptors (nAChR) and causing downstream effects that trigger reward pathways. Diversity in composition of neuronal nicotinic acetylcholine receptors affects binding of nicotine. In particular, the a3B4a5 neuronal nAChR has shown differences in nicotine binding affinity which this study hypothesized to be affected by allosteric binding of non-nicotine components of tobacco smoke. The cellular membrane affinity chromatography column technique was used to immobilize a3B4a5 receptors onto columns for screening of nicotine-free tobacco smoke condensates. In this study, we were able to detect allosteric binding of compounds in nicotine-free tobacco smoke condensates by testing competition with 3- hydroximorphinan, a known ligand that binds to the allosteric site of the a3B4a5 neuronal nAChR. We were able to identify a group of compounds from the nicotine-free tobacco smoke condensate sample that bind allosterically to a3B4a5 neuronal nAChRs. Binding of these compound to the allosteric site of the a3B4a5 neuronal nAChRs has potential to moderate binding affinity of nicotine and may lead to potential therapeutics for smoking cessation
Catharanthine Alkaloids are Noncompetitive Inhibitors of Muscle-Type Nicotinic Acetylcholine Receptors
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