Abstract:
:Exposure of brown fat cells to phenylephrine, an agonist of alpha-1 adrenergic receptors, activates a phospholipase A2 which releases arachidonic acid. Since receptor activation of phospholipase A2 requires calcium, experiments were undertaken to define more precisely the role played by calcium in the regulation of enzyme activity. In this study, adipocytes were loaded with the fluorescent calcium chelator quin2 in order to buffer intracellular calcium and block receptor stimulated changes in its concentration. When quin2 loaded adipocytes were incubated in buffer containing 0.10 mM calcium, the ability of phenylephrine to stimulate release of arachidonic acid was severely reduced. At an intracellular quin2 concentration of 6.6 mM stimulated arachidonic acid release was inhibited by more than 50% and at 13 mM it was completely blocked. In contrast, phenylephrine stimulation of inositol phosphate accumulation was unaffected by quin2. Quin2 also did not affect the liberation of arachidonic acid in response to exogenous phospholipase C, A23187 or forskolin. The intracellular calcium antagonist TMB-8 also inhibited phenylephrine-stimulation of arachidonic acid release and this effect was reversed by ionomycin. Basal phospholipase A2 activity was increased by introduction of high calcium concentrations into cells rendered permeable with digitonin, but phenylephrine still caused a further increase in enzyme activity. These findings show a selective inhibition of phenylephrine activation of phospholipase A2 by either the chelation of intracellular calcium with quin2 or by the calcium antagonist TMB-8 and suggest an essential role for intracellular calcium in alpha adrenergic stimulation of enzyme activity. However, because phenylephrine still stimulates enzyme activity in cells rendered permeable with digitonin, we suggest that the action of phenylephrine cannot be attributed solely to changes in intracellular calcium.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Schimmel RJdoi
10.1016/0898-6568(89)90069-7subject
Has Abstractpub_date
1989-01-01 00:00:00pages
607-16issue
6eissn
0898-6568issn
1873-3913pii
0898-6568(89)90069-7journal_volume
1pub_type
杂志文章abstract::High levels of VEGF and leptin are strongly linked to worse prognosis of breast cancer. Leptin signalling upregulates VEGF in human and mouse mammary tumor cells (MT), but the specific molecular mechanisms are largely unknown. Pharmacologic and genetic approaches were used to dissect the mechanism of leptin regulation...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.05.003
更新日期:2010-09-01 00:00:00
abstract::Timeless was originally identified in Drosophila as an essential component of circadian cycle regulation, where its function is tightly controlled at the protein level by tyrosine phosphorylation and subsequent degradation. In mammals, Timeless has also been implicated in circadian rhythms as well as cell cycle contro...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.12.009
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journal_title:Cellular signalling
pub_type: 杂志文章
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2013.01.027
更新日期:2013-05-01 00:00:00
abstract::Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase gene family that contributes to the invasiveness and metastasis in tumor progression. However, the role of LOXL2 in cellular signaling is incompletely understood. In this study, we investigated a possible mechanism of LOXL2 function in tumor metastases in v...
journal_title:Cellular signalling
pub_type: 杂志文章
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abstract::This review is intended to discuss recent developments in the molecular pharmacology of the alpha 1-adrenergic receptor (alpha 1-AR) subtypes. After a brief historical development, we will focus on the more contemporary issues having to do with this receptor family. Emphasis will be put on recent data regarding the cl...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
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更新日期:1996-08-01 00:00:00
abstract::Suppressor of fused (SUFU) is an essential negative regulator of the mammalian Hedgehog (HH) signaling pathway and its loss is associated with cancer development. On a cellular level, endogenous SUFU can mainly be detected in the cytoplasm and the nucleus. However, immunostaining of pancreatic cancer specimen revealed...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.08.037
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(89)90057-0
更新日期:1989-01-01 00:00:00
abstract::Transmembrane prostate androgen-induced protein (TMEPAI) is a type I transmembrane protein induced by several intracellular signaling pathways such as androgen, TGF-β, EGF, and Wnt signaling. It has been reported that TMEPAI functions to suppress TGF-β and androgen signaling but here, we report a novel function of TME...
journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2019.03.016
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.01.004
更新日期:2018-04-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.12.005
更新日期:2019-02-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00205-4
更新日期:2001-10-01 00:00:00
abstract::IFN-gamma and TNF-alpha are major proinflammatory cytokines implicated in islet beta-cell destruction, which results in type-1 diabetes; however, the underlying mechanism is not clear. Using pancreatic beta-cell line MIN6N8 cells, co-treatment with TNF-alpha and IFN-gamma, but neither cytokine alone, synergistically i...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.03.020
更新日期:2005-12-01 00:00:00
abstract::Calcineurin inhibitors such as cyclosporin A (CsA) and FK506 have been used in solid organ and hematopoietic stem cell transplantations to suppress immune function. However, these immunosuppresants are associated with severe endothelial dysfunction. We investigated whether CsA and FK506 induce endothelial dysfunction ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.05.008
更新日期:2013-09-01 00:00:00
abstract::The type II epithelial-mesenchymal transition (EMT) produces airway fibrosis and remodeling, contributing to the severity of asthma and chronic obstructive pulmonary disease. While numerous studies have been done on the mechanisms of the transition itself, few studies have investigated the system effects of EMT on sig...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.03.024
更新日期:2015-07-01 00:00:00
abstract::MAP Kinase Phosphatase-2 (MKP-2) is a dual specific nuclear phosphatase which is selective for both ERK and JNK, MAP kinases implicated in the regulation of apoptosis in response to genotoxic stress. Here we report the conditional expression of MKP-2 in human embryonic kidney cells 293. We demonstrate that Flag-WT-MKP...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.01.003
更新日期:2005-10-01 00:00:00
abstract::The maintenance of muscle mass is critical for health and issues associated with the quality of life. Over the last decade, extensive progress has been made with regard to our understanding of the molecules that regulate skeletal muscle mass. Not surprisingly, many of these molecules are intimately involved in the reg...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2011.07.013
更新日期:2011-12-01 00:00:00
abstract::Protease-activated receptor 1 (PAR1) is an unusual GPCR that interacts with multiple G protein subfamilies (G(q/11), G(i/o), and G(12/13)) and their linked signaling pathways to regulate a broad range of pathophysiological processes. However, the molecular mechanisms whereby PAR1 interacts with multiple G proteins are...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.01.011
更新日期:2012-06-01 00:00:00
abstract::It is well established that the IFN-gamma/STAT1 pathway plays an important role in the pancreatic beta-cell apoptosis that is observed in STZ-induced type 1 diabetes; however, the upstream regulatory proteins involved have not been understood. Here, we investigated whether activating transcription factor 3 (ATF3) affe...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.06.007
更新日期:2010-11-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(03)00132-3
更新日期:2004-02-01 00:00:00
abstract::Dysfunctional regulation of signaling pathways downstream of the insulin receptor plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. In this study we report both in vitro and in vivo experimental evidence for a role of Cullin-RING E3 ubiquitin ligase 7 (CRL7) in the regulation of insul...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.11.005
更新日期:2014-02-01 00:00:00
abstract::AMP-activated protein kinase (AMPK), an important regulator of energy homeostasis, is known to be activated during T cell activation. T cell activation by T cell receptor (TCR) engagement or its pharmacological mimics, PMA plus ionomycin (PMA/Io), induces immunomodulatory FasL and cyclooxygenase-2 (COX-2) expression. ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.01.015
更新日期:2012-06-01 00:00:00
abstract::The orthologous proteins of the stress-activated protein kinase-interacting 1 (Sin1) family have been implicated in several different signal transduction pathways. In this study, we have investigated the function of the full-length human Sin1 protein and a C-terminally truncated isoform, Sin1alpha, which is produced b...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.10.015
更新日期:2005-06-01 00:00:00
abstract::Protein kinase and phosphatase signaling cascade, coupled with other post-translational modifications, orchestrates temporal order of various events during cell division. Among the many mitotic kinases, Polo-like kinase 1 (PLK1) as a key regulator, participates in regulating mitosis from mitotic entry to cytokinesis. ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2010.07.003
更新日期:2011-01-01 00:00:00
abstract::The β-catenin signaling axis is critical for normal embryonic development and tissue homeostasis in adults. We have previously shown that extracellular enzyme transglutaminase 2 (TG2) activates β-catenin signaling in vascular smooth muscle cells (VSMCs). In this study, we provide several lines of evidence that TG2 fun...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.08.016
更新日期:2013-12-01 00:00:00
abstract::Monoamine oxidase-A (MAO-A) dysfunction has been historically associated with depression. Recently, depression as well as altered MAO-A expression have both been associated with a poor prognosis in cancers, although the mechanism involved remains ambiguous. For example, MAO-A mRNA is repressed across cancers, yet MAO-...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.08.005
更新日期:2014-12-01 00:00:00
abstract::Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative multifactorial disease characterized, like other diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) or frontotemporal dementia (FTD), by the degeneration of specific neuronal cell populations. Motor neuron loss is distinctive of ALS. However, ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.05.016
更新日期:2010-10-01 00:00:00
abstract::Protectin DX (PDX), which is a novel regulator of 5' adenosine monophosphate-activated protein kinase (AMPK), has recently gained attention for its ability to improve several metabolic diseases. However, the function of PDX in vascular endothelial cells remains unclear. To confirm the protective effects of PDX on endo...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.09.011
更新日期:2019-01-01 00:00:00
abstract::Ethanol, in millimolar concentrations, significantly modifies different transductive systems in human lymphocyte cultures. In particular, the presence of alcohol in the medium more than doubles the [Ca2+]i (from 70-90 to 200-250 nM), increasing Ca2+ fluxes from outside, and inhibits the active transport carried out by...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(93)90065-t
更新日期:1993-03-01 00:00:00
abstract::Differential regulation of PLC-beta 1 and -beta 2 by the G-protein alpha-subunit, G alpha 11, and by G-protein beta gamma-subunits was studied utilizing recombinant PLC-beta 1 and -beta 2. Rat PLC-beta 1 and human PLC-beta 2 were purified after recombinant baculovirus-mediated expression in Sf9 cells. The catalytic pr...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(95)00039-r
更新日期:1995-09-01 00:00:00