High-resolution imaging of the immunological synapse and T-cell receptor microclustering through microfabricated substrates.
AuthorsBiggs MJ, Milone MC, Santos LC, Gondarenko A, Wind SJ,
JournalJ R Soc Interface
PubMed ID21490003
'T-cell activation via antigen presentation is associated with the formation of a macromolecular membrane assembly termed the immunological synapse (IS). The genesis of the IS and the onset of juxtacrine signalling is characterized by the formation of cell membrane microclusters and the organization of such into segregated microdomains. A central ... More
Regulation of cytosolic phospholipase A2 (cPLA2alpha) and its association with cell proliferation in human lens epithelial cells.
AuthorsWang Y, Xing KY, Lou MF,
JournalInvest Ophthalmol Vis Sci
PubMed ID21896865
'To investigate the molecular mechanism for cytosolic phospholipase A2 (cPLA(2)a) regulation and its association to platelet-derived growth factor (PDGF)-induced cell proliferation. cPLA(2)a was examined using human lens epithelial (HLE) B3 cells. Reactive oxygen species (ROS) generation induced by PDGF was analyzed by luminescence assay. Cell proliferation was measured by cell ... More
20-Hydroxyeicosatetraenoic acid (20-HETE) is a novel activator of transient receptor potential vanilloid 1 (TRPV1) channel.
'TRPV1 is a member of the transient receptor potential ion channel family and is gated by capsaicin, the pungent component of chili pepper. It is expressed predominantly in small diameter peripheral nerve fibers and is activated by noxious temperatures >42 °C. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 4A/4F-derived metabolite ... More
Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice.
Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of ... More
Small molecule inhibition of PAX3-FOXO1 through AKT activation suppresses malignant phenotypes of alveolar rhabdomyosarcoma.
AuthorsJothi M, Mal M, Keller C, Mal AK,
Journal
PubMed ID24107448
Alveolar rhabdomyosarcoma comprises a rare highly malignant tumor presumed to be associated with skeletal muscle lineage in children. The hallmark of the majority of alveolar rhabdomyosarcoma is a chromosomal translocation that generates the PAX3-FOXO1 fusion protein, which is an oncogenic transcription factor responsible for the development of the malignant phenotype ... More
A selective cysteinyl leukotriene receptor 2 antagonist blocks myocardial ischemia/reperfusion injury and vascular permeability in mice.
AuthorsNi NC, Yan D, Ballantyne LL, Barajas-Espinosa A, St Amand T, Pratt DA, Funk CD,
JournalJ Pharmacol Exp Ther
PubMed ID21903747
Cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators that predominantly exert their effects by binding to cysteinyl leukotriene receptors of the G protein-coupled receptor family. CysLT receptor 2 (CysLT(2)R), expressed in endothelial cells of some vascular beds, has been implicated in a variety of cardiovascular functions. Endothelium-specific overexpression of human CysLT(2)R ... More
Phospholipase C signaling via the parathyroid hormone (PTH)/PTH-related peptide receptor is essential for normal bone responses to PTH.
AuthorsGuo J, Liu M, Yang D, Bouxsein ML, Thomas CC, Schipani E, Bringhurst FR, Kronenberg HM,
JournalEndocrinology
PubMed ID20501677
We have previously shown that differentiation of hypertrophic chondrocytes is delayed in mice expressing a mutated PTH/PTHrP receptor (PTHR) (called DSEL here) that stimulates adenylyl cyclase normally but fails to activate phospholipase C (PLC). To better understand the role of PLC signaling via the PTHR in skeletal and mineral homeostasis, ... More
NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection.
AuthorsHemrajani C, Berger CN, Robinson KS, Marchès O, Mousnier A, Frankel G,
JournalProc Natl Acad Sci U S A
PubMed ID20133763
The human pathogens enteropathogenic (EPEC) and enterohemorrhagic Escherichia coli and the related mouse pathogen Citrobacter rodentium subvert a variety of host cell signaling pathways via their plethora of type III secreted effectors, including triggering of an early apoptotic response. EPEC-infected cells do not develop late apoptotic symptoms, however. In this ... More
A novel in vitro model system for smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells.
AuthorsGuo X, Stice SL, Boyd NL, Chen SY,
JournalAm J Physiol Cell Physiol
PubMed ID23220114
The objective of this study was to develop a novel in vitro model for smooth muscle cell (SMC) differentiation from human embryonic stem cell-derived mesenchymal cells (hES-MCs). We found that hES-MCs were differentiated to SMCs by transforming growth factor-ß (TGF-ß) in a dose- and time-dependent manner as demonstrated by the ... More
HIV-1 Tat protein inhibits neurosecretion by binding to phosphatidylinositol 4,5-bisphosphate.
AuthorsTryoen-Tóth P, Chasserot-Golaz S, Tu A, Gherib P, Bader MF, Beaumelle B, Vitale N,
JournalJ Cell Sci
PubMed ID23178941
HIV-1 transcriptional activator (Tat) enables viral transcription and is also actively released by infected cells. Extracellular Tat can enter uninfected cells and affect some cellular functions. Here, we examine the effects of Tat protein on the secretory activity of neuroendocrine cells. When added to the culture medium of chromaffin and ... More
Calpain protects the heart from hemodynamic stress.
AuthorsTaneike M, Mizote I, Morita T, Watanabe T, Hikoso S, Yamaguchi O, Takeda T, Oka T, Tamai T, Oyabu J, Murakawa T, Nakayama H, Nishida K, Takeda J, Mochizuki N, Komuro I, Otsu K,
JournalJ Biol Chem
PubMed ID21795695
Calpains make up a family of Ca(2+)-dependent intracellular cysteine proteases that include ubiquitously expressed µ- and m-calpains. Both are heterodimers consisting of a distinct large catalytic subunit (calpain 1 for µ-calpain and calpain 2 for m-calpain) and a common regulatory subunit (calpain 4). The physiological roles of calpain remain unclear ... More
JNK1/2 regulates ER-mitochondrial Ca2+ cross-talk during IL-1ß-mediated cell death in RINm5F and human primary ß-cells.
AuthorsVerma G, Bhatia H, Datta M,
JournalMol Biol Cell
PubMed ID23615449
Elevated interleukin-1ß (IL-1ß) induces apoptosis in pancreatic ß-cells through endoplasmic reticulum (ER) stress induction and subsequent c-jun-N-terminal kinase 1/2 (JNK1/2) activation. In earlier work we showed that JNK1/2 activation is initiated before ER stress and apoptotic induction in response to IL-1ß. However, the detailed regulatory mechanisms are not completely understood. ... More
High-throughput drug profiling with voltage- and calcium-sensitive fluorescent probes in human iPSC-derived cardiomyocytes.
AuthorsBedut S, Seminatore-Nole C, Lamamy V, Caignard S, Boutin JA, Nosjean O, Stephan JP, Coge F,
JournalAm J Physiol Heart Circ Physiol
PubMed ID27199128
Cardiomyocytes derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) are increasingly used for in vitro assays and represent an interesting opportunity to increase the data throughput for drug development. In this work, we describe a 96-well recording of synchronous electrical activities from spontaneously beating hiPSC-derived ... More