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 induced apoptosis, correlated with the activation of the JNK/SAPK, which resulted in the production of reactive oxidative species (ROS) and loss of mitochondrial transmembrane potential (delta psi m). Additionally, cells transfected with wild-type JNK1 became more susceptible to apoptosis induced by TNF-alpha/IFN-gamma through ROS production and loss of delta psi m, while cascading apoptotic events were prevented in dominant-negative JNK1-transfected or JNK inhibitor SP600125-treated cells. As the antioxidant, N-acetyl-cysteine, failed to completely suppress apoptosis induced by TNF-alpha/IFN-gamma, an additional pathway was considered to be involved. The level of p53 was significantly increased through synergistic activation of JNK by TNF-alpha/IFN-gamma. Furthermore, the synergistic effect of TNF-alpha/IFN-gamma on apoptosis and ROS production was further potentiated by the overexpression of wild-type p53, but not with mutant p53. This synergistic activation of JNK/SAPK by TNF-alpha/IFN-gamma was also induced in insulin-expressing pancreatic islet cells, and increased ROS production and p53 level, which was significantly inhibited by SP600125. Collectively, these data demonstrate that TNF-alpha/IFN-gamma synergistically activates JNK/SAPK, playing an important role in promoting apoptosis of pancreatic beta-cell via activation of p53 pathway together with ROS.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Kim WH,Lee JW,Gao B,Jung MHdoi
10.1016/j.cellsig.2005.03.020subject
Has Abstractpub_date
2005-12-01 00:00:00pages
1516-32issue
12eissn
0898-6568issn
1873-3913pii
S0898-6568(05)00058-6journal_volume
17pub_type
杂志文章abstract：:We have demonstrated previously that chronic exposure to endothlin-1 enhances glucose transport in 3T3-L1 adipocytes via augmented GLUT1 mRNA and protein accumulation. In the present study, we further examined the combined effect of endothelin-1 (ET-1) and cAMP on glucose transport. In cells pretreated with ET-1 and 8...
journal_title：Cellular signalling
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journal_title：Cellular signalling
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.06.012
更新日期：2008-10-01 00:00:00
abstract：:In the canonical model of JAK/STAT signalling STAT transcription factors are activated by JAK mediated tyrosine phosphorylation following pathway stimulation by external cytokines. Activated STAT molecules then homo- or heterodimerise before translocating to the nucleus where they bind to DNA sequences within the prom...
journal_title：Cellular signalling
pub_type： 杂志文章
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abstract：:Therapeutic benefits and clinical application of paclitaxel for treating non-small cell lung cancers (NSCLCs) are extremely hampered due to the chemoresistance. A recent study found that fibronectin type III domain-containing protein 5 (FNDC5) was downregulated in NSCLCs cells and negatively correlated with the clinic...
journal_title：Cellular signalling
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doi：10.1016/j.cellsig.2020.109665
更新日期：2020-08-01 00:00:00
abstract：:Obesity is a widespread health problem that brings about various adipose tissue dysfunctions. The balance of energy storage and energy expenditure is critical for normal fat accumulation and lipid metabolism. Therefore, understanding the molecular basis of adipogenesis and thermogenesis is essential to maintain adipos...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2018.07.012
更新日期：2018-11-01 00:00:00
abstract：:Protein kinase D3 is a novel member of the serine/threonine kinase family PKD. The regulatory region of PKD contains a tandem repeat of C1 domains designated C1a and C1b that bind diacylglycerol and phorbol esters, and are important membrane targeting modules. Here, we investigate the activities of individual C1 domai...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.02.007
更新日期：2005-11-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.02.003
更新日期：2014-06-01 00:00:00
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journal_title：Cellular signalling
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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.2017.08.003
更新日期：2017-11-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
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更新日期：2020-06-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.09.016
更新日期：2009-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109803
更新日期：2020-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2004.06.010
更新日期：2005-02-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.11.003
更新日期：2009-03-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(97)00179-4
更新日期：1998-06-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2018.12.009
更新日期：2019-03-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.04.003
更新日期：2014-08-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2009.02.012
更新日期：2009-08-01 00:00:00
abstract：:Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that is known to mediate diverse cellular responses including cell growth, survival, and migration. Most of these effects have been attributed to its binding to a specific subfamily of G protein-coupled receptors (GPCR), namely S1P(1-5). Recent studi...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2004.09.013
更新日期：2005-03-01 00:00:00
abstract：:Glycogen synthase kinase 3beta (GSK3beta) is implicated in many biological events, including embryonic development, cell differentiation, apoptosis, and the insulin response. GSK3beta also plays a key role in the Wnt/beta-catenin pathway. The master regulator of the pigmentation microphthalmia-associated transcription...
journal_title：Cellular signalling
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doi：10.1016/j.cellsig.2008.06.001
更新日期：2008-10-01 00:00:00
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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
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2013.03.025
更新日期：2013-08-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2017.10.009
更新日期：2018-01-01 00:00:00
abstract：:Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults with median survival time of 14.6 months. A small fraction of cancer stem cells (CSC) initiate and maintain tumors thus driving glioma tumorigenesis and being responsible for resistance to classical chemo- and radio-therapies...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.08.020
更新日期：2014-12-01 00:00:00
abstract：:Oxidative stress is an increase in the reduction potential or a large decrease in the reducing capacity of the cellular redox couples. A particularly destructive aspect of oxidative stress is the production of reactive oxygen species (ROS), which include free radicals and peroxides. Some of the less reactive of these ...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2007.04.009
更新日期：2007-09-01 00:00:00
abstract：:Heterotrimeric (alphabetagamma) G(s) mediates agonist-induced stimulation of adenylyl cyclase (AC). Cholera toxin (CTx) will ADP-ribosylate the alpha-subunit of G(s) (G(s)alpha). G(s)alpha-deficient cyc(-) membranes were "stripped" of Gbeta. When the stripped cyc(-) were incubated with G(s)alpha and/or Gbetagamma, eac...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(99)00078-9
更新日期：2000-02-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2004.12.003
更新日期：2005-09-01 00:00:00
abstract：:Both canonical Wnt/beta-catenin and TGFbeta/Smad signaling pathways coordinately regulate pattern formation during embryogenesis as well as tumor progression. Evidence of cross-talk between these two pathways has been reported. Here we demonstrated that the Activin-like kinase 4 (Alk4)/Smad2 pathway facilitates the tr...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.05.003
更新日期：2008-09-01 00:00:00
abstract：:The long cyclic AMP (cAMP)-specific phosphodiesterase isoform, PDE4A5 (PDE4A subfamily isoform variant 5), when transiently expressed in COS-7 cells, was shown in subcellular fractionation studies to be associated with both membrane and cytosol fractions, with immunofluorescence analyses identifying PDE4A5 as associat...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(01)00264-9
更新日期：2002-05-01 00:00:00
