Cell death and autophagy under oxidative stress: roles of poly(ADP-Ribose) polymerases and Ca(2+).
AuthorsWyrsch P, Blenn C, Bader J, Althaus FR,
JournalMol Cell Biol
PubMed ID22751932
On the cellular level, oxidative stress may cause various responses, including autophagy and cell death. All of these outcomes involve disturbed Ca(2+) signaling. Here we show that the nuclear enzymes poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 control cytosolic Ca(2+) shifts from extracellular and intracellular sources associated with autophagy or cell ... More
The Nef protein of human immunodeficiency virus is a broad-spectrum modulator of chemokine receptor cell surface levels that acts independently of classical motifs for receptor endocytosis and Galphai signaling.
AuthorsMichel N, Ganter K, Venzke S, Bitzegeio J, Fackler OT, Keppler OT
JournalMol Biol Cell
PubMed ID16775006
'Chemokine receptors (CKRs) are important physiological mediators of immune defense, inflammatory responses, and angiogenesis, and they have also been implicated in a number of viral disease processes. Here, we report that the Nef protein of human immunodeficiency virus (HIV) reduces cell surface levels of eight different members of the CC- ... More
Development and validation of a cell-based high-throughput screening assay for TRPM2 channel modulators.
AuthorsSong Y, Buelow B, Perraud AL, Scharenberg AM,
JournalJ Biomol Screen
PubMed ID18057180
'TRPM2 is a member of the transient receptor potential melastatin (TRPM)-related ion channel family. The activation of TRPM2 induced by oxidative/nitrosative stress leads to an increase in intracellular free Ca(2+). Although further progress in understanding TRPM2''s role in cell and organism physiology would be facilitated by isolation of compounds able ... More
Fc receptor-like 5 inhibits B cell activation via SHP-1 tyrosine phosphatase recruitment.
AuthorsHaga CL, Ehrhardt GR, Boohaker RJ, Davis RS, Cooper MD
JournalProc Natl Acad Sci U S A
PubMed ID17522256
'The Fc receptor-like protein 5 (FCRL5) on B cells has both an immunoreceptor tyrosine-based activation motif (ITAM)-like sequence and two consensus immunoreceptor tyrosine-based inhibitory motifs (ITIM) in its cytoplasmic region. To evaluate its signaling potential, we expressed constructs for chimeric molecules composed of the cytoplasmic region of FCRL5 and the ... More
Pertussis toxin signals through the TCR to initiate cross-desensitization of the chemokine receptor CXCR4.
AuthorsSchneider OD, Weiss AA, Miller WE,
JournalJ Immunol
PubMed ID19380820
Pertussis toxin (PTx) has been shown to exert a variety of effects on immune cells independent of its ability to ADP-ribosylate G proteins. Of these effects, the binding subunit of PTx (PTxB) has been shown to block signaling via the chemokine receptor CCR5, but the mechanism involved in this process ... More
Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation.
AuthorsKang JS, Tian JH, Pan PY, Zald P, Li C, Deng C, Sheng ZH,
JournalCell
PubMed ID18191227
Proper distribution of mitochondria within axons and at synapses is critical for neuronal function. While one-third of axonal mitochondria are mobile, a large proportion remains in a stationary phase. However, the mechanisms controlling mitochondrial docking within axons remain elusive. Here, we report a role for axon-targeted syntaphilin (SNPH) in mitochondrial ... More
A FLIPR-based assay to assess potency and selectivity of inhibitors of the TEC family kinases Btk and Itk.
Bruton's tyrosine kinase (Btk) and interleukin-2-inducible T cell kinase (Itk) are members of the TEC family of nonreceptor tyrosine kinases and are expressed primarily in B and T cells, respectively. Both kinases are critically involved in lymphocyte development and signal transduction. In particular, Btk and Itk regulate calcium mobilization subsequent ... More
Reinforcement versus fluidization in cytoskeletal mechanoresponsiveness.
Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or ... More
TRPV6 mediates capsaicin-induced apoptosis in gastric cancer cells--Mechanisms behind a possible new "hot" cancer treatment.
AuthorsChow J, Norng M, Zhang J, Chai J
JournalBiochim Biophys Acta
PubMed ID17292493
Capsaicin is an organic compound in chili peppers which are consumed by over one quarter of the world's population daily. Studies have shown that capsaicin can induce apoptosis in some cancer cells by unknown mechanisms. In this study, both gastric cancer and normal epithelial cells were treated with capsaicin and ... More
Multiplexing Fluo-4 NW and a GeneBLAzer transcriptional assay for high-throughput screening of G-protein-coupled receptors.
AuthorsHanson BJ
JournalJ Biomol Screen
PubMed ID16831860
Activation of G-protein-coupled receptors (GPCRs) leads to a cascade of signaling events, including calcium mobilization and downstream transcriptional activation of various proteins. Two commonly used methods of high-throughput screening for GPCRs include calcium-sensitive dyes, such as Fluo-4 NW, and reporter gene assays, such as beta-lactamase. To determine whether the advantages ... More
Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death.
AuthorsBorradaile NM, Han X, Harp JD, Gale SE, Ory DS, Schaffer JE
JournalJ Lipid Res
PubMed ID16960261
Cell dysfunction and death induced by lipid accumulation in nonadipose tissues, or lipotoxicity, may contribute to the pathogenesis of obesity and type 2 diabetes. However, the mechanisms leading to lipotoxic cell death are poorly understood. We recently reported that, in Chinese hamster ovary (CHO) cells and in H9c2 cardiomyoblasts, lipid ... More
Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes.
Authors
JournalNat Mater
PubMed ID22019944
Protective responses to sublytic complement in the retinal pigment epithelium.
Authors
JournalProc Natl Acad Sci U S A
PubMed ID27432952
The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super enhancers to promote direct reprogramming.
Authors
JournalNat Cell Biol
PubMed ID33941892
Nicotinamide Pathway-Dependent Sirt1 Activation Restores Calcium Homeostasis to Achieve Neuroprotection in Spinocerebellar Ataxia Type 7.
Authors
JournalNeuron
PubMed ID31859031
Microfluidic local perfusion chambers for the visualization and manipulation of synapses.
Authors
JournalNeuron
PubMed ID20399729
Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors.
Authors
JournalMol Cell
PubMed ID34582793
Cytochrome c Oxidase Activity Is a Metabolic Checkpoint that Regulates Cell Fate Decisions During T Cell Activation and Differentiation.
Authors
JournalCell Metab
PubMed ID28591633
Farnesoid X Receptor Regulation of the NLRP3 Inflammasome Underlies Cholestasis-Associated Sepsis.
Authors
JournalCell Metab
PubMed ID28380377
Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel.
Authors
JournalSci Transl Med
PubMed ID31578243
Zinc ion flux during mammalian sperm capacitation.