Abstract:
:Microglia play a prominent role in the brain's inflammatory response to injury or infection by migrating to affected locations, secreting inflammatory molecules, and phagocytosing damaged tissue. However, because severe or chronic neuroinflammation exacerbates many neurological conditions, controlling microglia actions may provide therapeutic benefits in a diverse array of diseases. Since glycogen synthase kinase-3 (GSK3) promotes inflammatory responses in peripheral immune cells, we investigated if inhibitors of GSK3 attenuated microglia responses to inflammatory stimuli. Treatment of BV-2 microglia with GSK3 inhibitors greatly reduced the migration of microglia in both a scratch assay and in a transwell migration assay. Treatment of BV-2 microglia with lipopolysaccharide (LPS) stimulated the production of interleukin-6 and increased the expression of inducible nitric oxide synthase (iNOS) and NO production. Each of these microglia responses to inflammatory stimulation were greatly attenuated by GSK3 inhibitors. However, GSK3 inhibitors did not cause a general impairment of microglia functions, as the LPS-induced stimulated expression of cyclooxygenase-2 was unaltered. Regulation of microglia functions were also evident in cultured mouse hippocampal slices where GSK3 inhibitors reduced cytokine production and microglial migration, and provided protection from inflammation-induced neuronal toxicity. These findings demonstrate that GSK3 promotes microglial responses to inflammation and that the utilization of GSK3 inhibitors provides a means to limit the inflammatory actions of microglia.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Yuskaitis CJ,Jope RSdoi
10.1016/j.cellsig.2008.10.014subject
Has Abstractpub_date
2009-02-01 00:00:00pages
264-73issue
2eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00324-0journal_volume
21pub_type
杂志文章abstract::Ceramide 1-phosphate (C1P) is a bioactive sphingolipid that is implicated in the regulation of cell homeostasis and the control of inflammation. It is mitogenic for fibroblasts and macrophages, and has been described as potent inhibitor of apoptosis. Using RAW 264.7 macrophages we have now discovered a new biological ...
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
abstract::Suppressor of Fused (SuFu) plays a conservative role in the regulation of the Gli transcription factors within the Hedgehog (Hh) signaling pathway. Despite the central importance of SuFu in the Hh pathway, little is known about its regulation. Here, we performed a GAL4-based yeast two-hybrid screen using human SuFu as...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.06.010
更新日期:2016-09-01 00:00:00
abstract::Mitogen-activated protein (MAP) kinase cascades are signal transduction pathways that play pivotal regulatory roles in the biosynthesis of pro-inflammatory cytokines. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP family, is essential for the dephosphorylation/deactivation of MAP kinases p38 and JNK. ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2007.03.013
更新日期:2007-07-01 00:00:00
abstract::Binding of fibroblast growth factor (FGF) to the high affinity receptor-1 (FGFR-1) leads to activation of its endogenous tyrosine kinase activity. A number of substrates for the FGFR-1 kinase have been identified. Among those, FGF receptor-substrate-2 (FRS-2) was identified by virtue of its interaction with p13suc, a ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2003.09.007
更新日期:2004-04-01 00:00:00
abstract::Perivascular adipocyte (PVAC) biofunctions were closely related to cardiovascular diseases; its specific biological mechanisms remained unclear. How to adjust PVAC functions of vascular cells is an important topic. The present study was designed to investigate whether FAK/Pyk2 and ERK1/2 MAPK signaling pathways partic...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.09.017
更新日期:2014-12-01 00:00:00
abstract::In Galpha(z)-deficient mice, survival of sympathetic neurons is significantly attenuated in the presence of pertussis toxin (PTX). This suggests that G(i/o) proteins may have distinct roles in neuronal survival. Here, we investigated the possible involvement of G(i/o) proteins in nerve growth factor (NGF)-induced pro-...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.11.008
更新日期:2005-07-01 00:00:00
abstract::Janus kinase 2 (Jak2) has a pivotal role in erythropoietin (Epo) signaling pathway, including erythrocyte differentiation and Stat5 activation. In the course of screening for critical phosphorylation of tyrosine residues in Jak2, we identified tyrosine 913 (Y(913)) as a novel and functional phosphorylation site, which...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.07.008
更新日期:2008-11-01 00:00:00
abstract::Arap3 is a phosphoinositide (PI) 3 kinase effector that serves as a GTPase activating protein (GAP) for both Arf and Rho G-proteins. The protein has multiple pleckstrin homology (PH) domains that bind preferentially phosphatidyl-inositol-3,4,5-trisphosphate (PI(3,4,5,)P3) to induce translocation of Arap3 to the plasma...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.12.015
更新日期:2007-06-01 00:00:00
abstract::The phosphatidylinositol (PI) 3-kinase family of enzymes is now known to be regulated by several different upstream pathways in response to virtually all growth factors and cytokines. In the past few years, the phosphoinositides phosphorylated at the 3-OH position of the inositol ring have been shown to be lipid secon...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(97)00129-0
更新日期:1998-04-01 00:00:00
abstract::Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2017.10.017
更新日期:2018-01-01 00:00:00
abstract::We analyse the role of the G proteins in regulating collagen gene expression by measuring collagen alpha 1(I) mRNA levels in cultured hepatic stellate cells in basal conditions and after stimulating or inhibiting the major intracellular signalling pathways. Stimulation of Gs protein and adenylyl cyclase or the additio...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(97)00036-3
更新日期:1998-03-01 00:00:00
abstract::Endoplasmic reticulum (ER) stress activated by perturbations in ER homeostasis induces the unfolded protein response (UPR) with chaperon Grp78 as the key activator of UPR signalling. The aim of UPR is to restore normal ER function; however prolonged or severe ER stress triggers apoptosis of damaged cells to ensure pro...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.04.008
更新日期:2010-09-01 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::Sustained activation of Akt kinase acts as a focal regulator to increase cell growth and survival, which causes tumorigenesis including breast cancer. Statins, potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, display anticancer activity. The molecular mechanisms by which statins block cancer cell ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.12.010
更新日期:2010-05-01 00:00:00
abstract::Understanding how cells integrate signals from a variety of chemically diverse information-containing molecules into complex, orchestrated responses such as cell proliferation, differentiation and apoptosis is an overarching goal of cell biology. The ligand molecules that act upon cell surface receptors include those ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(97)00194-0
更新日期:1998-09-01 00:00:00
abstract::A pathological hallmark of Alzheimer's disease (AD) is the aggregation of amyloid-β peptides (Aβ) into fibrils, leading to deposits in cerebral parenchyma and vessels known as cerebral amyloid angiopathy (CAA). Platelets are major players of hemostasis but are also implicated in AD. Recently we provided strong evidenc...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.06.015
更新日期:2018-10-01 00:00:00
abstract::Analysis of the genomic sequences, cDNAs and expressed sequence tags (ESTs) in human and mouse for the 12 genes of the gamma subunits of the heterotrimeric G proteins has allowed us to identify the common versus unique elements of the organization and expression of the members of this important gene family. All of the...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.04.011
更新日期:2006-02-01 00:00:00
abstract::Although increasing evidence demonstrated that deregulation of mircoRNA-503 (miRNA-503) contributes to tumorigenesis, little is known about the biological role and intrinsic regulatory mechanisms of miR-503 in prostate cancer (PCa). In present study, we found that miR-503 was significantly downregulated in advanced PC...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.06.002
更新日期:2016-09-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high rate of mortality. Highly upregulated in liver cancer (HULC), the specifically overexpressed long non-coding RNA in human HCC, plays important roles in promoting the growth and metastasis of HCC cells. So downregulating HULC will be bene...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109720
更新日期:2020-10-01 00:00:00
abstract::In humans, thromboxane (TX) A(2) signals through the TPalpha and TPbeta isoforms of the TXA(2) receptor that exhibit common and distinct roles. For example, Gq/phospholipase (PL)Cbeta signaling by TPalpha is directly inhibited by the vasodilators prostacyclin and nitric oxide (NO) whereas that signaling by TPbeta is u...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.04.006
更新日期:2008-08-01 00:00:00
abstract::Caffeine and ryanodine triggered an increase in [Ca2+]i (73 +/- 22 and 61 +/- 18 nM, respectively) in Jurkat cell populations that was independent of external Ca2+. In individual cells, caffeine and ryanodine induced Ca2+ spikes. Jurkat cell populations initially exposed to caffeine did not respond further to ryanodin...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(96)00141-6
更新日期:1997-02-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative illness and the leading cause of dementia in the elderly. The accumulation of amyloid-β peptide (Aβ) is a well-known pathological hallmark associated with the disease. However, Aβ is only one of several metabolites produced by β- and γ-secretase actions on the transmembr...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2011.10.007
更新日期:2012-02-01 00:00:00
abstract::MAPK signalling is a complex process not only requiring the core components Raf, MEK and Erk, but also many proteins like the scaffold protein KSR and several kinases to specifically localize, modulate and fine-tune the outcome of the pathway in a cell context specific manner. In mammals, protein kinase CK2 was shown ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.01.013
更新日期:2011-05-01 00:00:00
abstract::GRB2 related adaptor protein downstream of Shc (GADS) is a member of the GRB2 family of adaptors and is critical for TCR-induced signaling. The current model is that GADS recruits SLP-76 to the LAT complex, which facilitates the phosphorylation of SLP-76, the activation of PLC-γ1, T cell adhesion and cytokine producti...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.01.012
更新日期:2015-04-01 00:00:00
abstract::Ketone bodies β-hydroxybutyrate (BHB) and acetoacetate are important metabolic substrates for energy production during prolonged fasting. However, BHB also has signaling functions. Through several metabolic pathways or processes, BHB modulates nutrient utilization and energy expenditure. These findings suggest that BH...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2016.04.005
更新日期:2016-08-01 00:00:00
abstract::Recent studies have demonstrated that long non-coding RNAs (lncRNAs) play critical roles in cancer development and progression. However, the mechanism by which lncRNAs contribute to colorectal cancer remains unclear. In this study, we identified the lncRNA, DANCR, which was upregulated in colorectal cancer. The upregu...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109502
更新日期:2020-03-01 00:00:00
abstract::DMSO differentiated U937 cells responded to 10(-6) M LTD4, LTB4 and FMLP with an increase in both InsP formation and [Ca2+]i. FMLP caused a greater rise in InsPs than either LTD4 or LTB4, which were equivalent. LTD4, however, caused a greater increase in [Ca2+]i than LTB4 (4-fold) or FMLP. The FMLP [Ca2+]i and InsP re...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(90)90078-o
更新日期:1990-01-01 00:00:00
abstract::JNK proteins are conserved stress-activated MAP kinases. In C. elegans, the JNK-homolog KGB-1 plays essential roles in protection from heavy metals and protein folding stress. However, the contributions of KGB-1 are age-dependent, providing protection in larvae, but reducing stress resistance and shortening lifespan i...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.11.010
更新日期:2017-01-01 00:00:00
abstract::Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is essential for the immortalization of human B cells and is linked etiologically to several human tumors. LMP1 is an integral membrane protein which acts like a constitutively active receptor. It binds tumor necrosis factor (TNF)-receptor-associated fa...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.03.014
更新日期:2004-10-01 00:00:00
abstract::Lithium is an anti-depressant drug that also possesses immunomodulatory functions. The anti-inflammatory effect of lithium is thought to involve activation of the transcription factor CREB, although the underlying mechanism is incompletely understood. We show here that in macrophages lithium stimulates Tpl2, a MAP kin...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.12.010
更新日期:2009-04-01 00:00:00