A5101892562- Phosphodiesterase function and regulation
- Protein Tyrosine Phosphatases
- Receptor Mechanisms and Signaling
- Sirtuins and Resveratrol in Medicine
- Cholinesterase and Neurodegenerative Diseases
- Adipose Tissue and Metabolism
- Calcium signaling and nucleotide metabolism
- Synthesis and Catalytic Reactions
- Heart Failure Treatment and Management
- Pancreatic function and diabetes
- Genetics, Aging, and Longevity in Model Organisms
- Protein Kinase Regulation and GTPase Signaling
- Galectins and Cancer Biology
- Signaling Pathways in Disease
- Renin-Angiotensin System Studies
- Autophagy in Disease and Therapy
- Alkaline Phosphatase Research Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Orthopaedic implants and arthroplasty
- Apelin-related biomedical research
- Blood Pressure and Hypertension Studies
- Ion Transport and Channel Regulation
- Glycosylation and Glycoproteins Research
- Glycogen Storage Diseases and Myoclonus
- Neuropeptides and Animal Physiology
Regional Research Institute of Unani Medicine
2023
Central Research Institute
2023
Babasaheb Bhimrao Ambedkar Bihar University
2022
Institute of Medical Sciences
2022
Sidra Medical and Research Center
2021
National Heart Lung and Blood Institute
2009-2019
National Institutes of Health
2007-2019
Teerthanker Mahaveer Medical College & Research Centre
2017
Pulmonary Associates
2015
VA Salt Lake City Healthcare System
2012
Tumor necrosis factor-α (TNF-α) stimulates lipolysis in human adipocytes. However, the mechanisms regulating this process are largely unknown. We demonstrate that TNF-α increases differentiated adipocytes by activation of mitogen-activated protein kinase (MEK), extracellular signal-related (ERK), and elevation intracellular cAMP. activated ERK increased lipolysis; these effects were inhibited two specific MEK inhibitors, PD98059 U0126. treatment caused an electrophoretic shift perilipin from...
Obese human subjects have increased protein-tyrosine phosphatase (PTPase) activity in adipose tissue that can dephosphorylate and inactivate the insulin receptor kinase. To extend these findings to skeletal muscle, we measured PTPase muscle particulate fraction cytosol from a series of lean controls, insulin-resistant obese (body mass index > 30) nondiabetic subjects, individuals with non-insulin-dependent diabetes. activities subcellular fractions were 140-170% level controls (P < 0.05). In...
cAMP is an important regulator of myocardial function, and regulation hydrolysis by cyclic nucleotide phosphodiesterases (PDEs) a critical determinant the amplitude, duration, compartmentation cAMP-mediated signaling. The role different PDE isozymes, particularly PDE3A vs PDE3B, in heart function remains unclear.
Rationale: Baseline contractility of mouse hearts is modulated in a phosphatidylinositol 3-kinase-γ–dependent manner by type 4 phosphodiesterases (PDE4), which regulate cAMP levels within microdomains containing the sarcoplasmic reticulum (SR) calcium ATPase 2a (SERCA2a). Objective: The goal this study was to determine whether PDE4D regulates basal cardiac contractility. Methods and Results: At 10 12 weeks age, baseline PDE4D-deficient (PDE4D −/− ) mice elevated vivo Langendorff perfused...
Cyclic nucleotide phosphodiesterase 3A (PDE3) regulates cAMP-mediated signaling in the heart, and PDE3 inhibitors augment contractility patients with heart failure. Studies mice showed that PDE3A, not PDE3B, is subfamily responsible for these inotropic effects murine PDE3A1 associates sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2), phospholamban (PLB), AKAP18 a multiprotein signalosome human (SR). Immunohistochemical staining demonstrated PDE3A co-localizes Z-bands of cardiac myocytes...
Although inhibition of cyclic nucleotide phosphodiesterase type 3 (PDE3) has been reported to protect rodent heart against ischemia/reperfusion (I/R) injury, neither the specific PDE3 isoform involved nor underlying mechanisms have identified. Targeted disruption subfamily B (PDE3B), but not A (PDE3A), protected mouse from I/R injury in vivo and vitro, with reduced infarct size improved cardiac function. The cardioprotective effect PDE3B(-/-) was reversed by blocking cAMP-dependent PKA...
PDE3A cyclic nucleotide phosphodiesterases regulate cAMP- and cGMP-mediated intracellular signaling in cardiac myocytes. We used antibodies to different regions of demonstrate the presence three isoforms these cells. These isoforms, whose apparent molecular weights are 136,000, 118,000, 94,000 ("PDE3A-136," "PDE3A-118," "PDE3A-94"), identical save for deletion lengths N-terminal sequence containing two membrane-association domains sites phosphorylation/activation by protein kinase B ("PK-B")...
Protein-tyrosine phosphatases (PTPases) have an essential role in the regulation of steady-state phosphorylation insulin receptor and other proteins signalling pathway. To examine whether increased PTPase activity is associated with adipose tissue resistance human obesity we measured enzyme towards homogenates subcutaneous from a series six lean nondiabetic, obese (body mass index > 30) subjects. The subjects had mean 1.74-fold increase (P < 0.0001) striking positive correlation by linear...
Three isoforms of PDE3 (cGMP-inhibited) cyclic nucleotide phosphodiesterase regulate cAMP content in different intracellular compartments cardiac myocytes response to signals. We characterized the catalytic activity and inhibitor sensitivity these by using recombinant proteins. determined their contribution hydrolysis cytosolic microsomal fractions human myocardium at 0.1 1.0 μm absence presence Ca2+/calmodulin. examined effects cGMP on fractions. PDE3A-136, PDE3A-118, PDE3A-94 have similar...
The receptor-type protein-tyrosine phosphatase LAR (for leukocyte common antigen-related) has been implicated as a physiological regulator of the insulin receptor. To demonstrate functional interaction between and receptor, we incubated CHO cells overexpressing human receptor with an antibody to extracellular domain found 47% decrease in autophosphorylation kinase activity. A physical association was then shown by immunoprecipitation from cell lysates immunoblotting or <i>vice versa</i>. Up...
The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, gain of does not increase function, which raises a question about the central role action. Moreover, it is believed that metabolic effects occur independently AMP-activated protein kinase (AMPK), an important regulator function. Here, we show activates AMPK Sirt1-independent manner and inhibiting cAMP degrading phosphodiesterase (PDE) competitive manner....
Abstract Understanding mechanisms by which a population of beige adipocytes is increased in white adipose tissue (WAT) reflects potential strategy the fight against obesity and diabetes. Cyclic adenosine monophosphate (cAMP) very important development phenotype activation its thermogenic program. To study effects cyclic nucleotides on energy homeostatic mechanisms, mice were generated targeted inactivation nucleotide phosphodiesterase 3b (Pde3b) gene, encodes PDE3B, an enzyme that catalyzes...
Abstract Activation of inflammation in white adipose tissue (WAT), includes infiltration/expansion WAT macrophages, contributes pathogenesis obesity, insulin resistance and metabolic syndrome. The inflammasome comprises an intracellular sensor (NLR), caspase-1 the adaptor ASC. Inflammasome activation leads to maturation processing IL1β, contributing many disorders directing adipocytes a more insulin-resistant phenotype. Ablation PDE3B prevents by reducing expression NLRP3, caspase-1, ASC,...