Abstract:
:We found that CKD712, an S enantiomer of YS49, strongly inhibited inducible nitric oxide synthase (iNOS) and NO induction but showed a weak inhibitory effect on cyclooxygenase-2 (COX-2) and PGE(2) induction in LPS-stimulated RAW 264.7 cells. We, therefore, investigated the molecular mechanism(s) responsible for this by using CKD712 in LPS-activated RAW264.7 cells. Treatment with either SP600125, a specific JNK inhibitor or TPCK, a NF-kappaB inhibitor, but neither ERK inhibitor PD98059 nor p38 inhibitor SB203580, significantly inhibited LPS-mediated iNOS and COX-2 induction. CKD712 inhibited NF-kappaB (p65) activity and translocation but failed to prevent JNK activation. However, AG490, a specific JAK-2/STAT-1 inhibitor, efficiently prevented LPS-mediated iNOS induction but not the induction of COX-2, and CKD712 completely blocked STAT-1 phosphorylation by LPS, suggesting that the NF-kappaB and JAK-2/STAT-1 pathways but not the JNK pathway are important for CKD712 action. Interestingly, CKD712 induced heme oxygenase 1 (HO-1) gene expression in LPS-treated cells. LPS-induced NF-kappaB and STAT-1 activation was partially prevented by HO-1 overexpression. Furthermore, HO-1 siRNA partly reversed not only the LPS-induced NF-kappaB activation and STAT-1 phosphorylation but also inhibition of these actions by CKD 712. Additionally, silencing HO-1 by siRNA prevented CKD712 from inhibiting iNOS expression but not COX-2. When examined plasma NO and PGE(2) levels and iNOS and COX-2 protein levels in lung tissues of mice injected with LPS (10 mg/kg), pretreatment with CKD712 greatly prevented NO and iNOS induction in a dose-dependent manner and slightly affected PGE(2) and COX-2 production as expected. Taken together, we conclude that inhibition of JAK-2/STAT-1 pathways by CKD 712 is critical for the differential inhibition of iNOS and COX-2 by LPS in vitro and in vivo where HO-1 induction also contributes to this by partially modulating JAK-2/STAT-1 pathways.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Tsoyi K,Kim HJ,Shin JS,Kim DH,Cho HJ,Lee SS,Ahn SK,Yun-Choi HS,Lee JH,Seo HG,Chang KCdoi
10.1016/j.cellsig.2008.06.012subject
Has Abstractpub_date
2008-10-01 00:00:00pages
1839-47issue
10eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00186-1journal_volume
20pub_type
杂志文章abstract::Cell cycle progression from G2 phase into mitosis is regulated by a complex network of mechanisms, all of which finally control the timing of Cyclin B/CDK1 activation. PLK1 regulates a network of events that contribute to regulating G2/M phase progression. Here we have used a proteomics approach to identify proteins t...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.08.009
更新日期:2015-11-01 00:00:00
abstract::Hydrogen peroxide (H(2)O(2)) mediates induction of cytotoxicity in various cell types. GSK-3beta has been found to participate in a number of signaling pathways, including cell proliferation and cell death. In the present study, we show that GSK-3beta is rapidly dephosphorylated and activated in response to H(2)O(2) t...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.06.001
更新日期:2006-05-01 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::Cd(2+) exposure increases the risk of cancer in humans and animals. In this report, we have studied the effect of Cd(2+) on signal transduction and Ca(2+) mobilization in murine macrophages. At micromolar concentrations, Cd(2+) significantly increased cell division as judged by [3H]thymidine uptake and cell counts. Cd...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00268-6
更新日期:2002-04-01 00:00:00
abstract::Understanding receptor activation is important for disease intervention. Activation of the receptor tyrosine kinase c-KIT is involved in numerous diseases including melanoma, mastocytosis, multiple myeloma and gastrointestinal stromal tumors. To better understand the regulation of activation, we studied the two c-KIT ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.07.011
更新日期:2013-11-01 00:00:00
abstract::The human ether-a-go-go related gene (HERG) potassium channel has elicited intense scientific interest due to its role in cardiac repolarization and its association with arrhythmia and sudden cardiac death. Increasing evidence indicates the involvement of HERG channels in the pathophysiology of cancer. In the present ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.09.010
更新日期:2010-01-01 00:00:00
abstract::13-(S)-Hydroxyoctadecadienoic acid (13-HODE), the lipoxygenase metabolite of linoleic acid, has been shown to reverse the epidermal hyperproliferation induced by topical application of docosahexaenoic acid (DNA, 22:6 n-3) on guinea pig skin. Our initial studies demonstrated that 13-HODE exerts a selective inhibition o...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(97)00099-5
更新日期:1998-02-01 00:00:00
abstract::Protein Kinase B (PKB/Akt) is a key regulator of cell proliferation, motility and survival. The activation status of PKB is regulated by phosphatidylinositol 3-kinase (PI3K) via the synthesis of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3, PIP3). PTEN antagonises PI3K by degrading PIP3 to phosphatidylinosito...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.05.029
更新日期:2007-01-01 00:00:00
abstract::We previously showed that an increase of cellular Bcl-xL mediates acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and knockdown of Bcl-xL expression greatly sensitized TRAIL-induced cytotoxicity. Here, we show that Daxx downregulation increases the anti-tumorigenic activity throu...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.02.028
更新日期:2015-06-01 00:00:00
abstract::Both type I interferons (IFNs) and interferon regulatory factors (IRFs) are well characterized in viral infections, whereas they are far less studied in bacterially activated toll-like receptor (TLR) pathways. Here, we studied the involvement of IRF1 and IRF2 in TLR2-mediated responses. In mouse macrophages, IRF2 was ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.06.017
更新日期:2008-10-01 00:00:00
abstract::Tribbles 3 homolog (TRB3) is recently identified as a scaffold-like regulator of various signal transducers and has been implicated in several processes including insulin signaling, NF-kappaB signaling, lipid metabolism and BMP signaling. To further understand cellular mechanisms of TRB3 regulation, we performed a yea...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.01.010
更新日期:2008-05-01 00:00:00
abstract::Protein kinase CK2 is a highly conserved, pleiotropic, protein serine/threonine kinase that is essential for life in eukaryotes. CK2 has been implicated in diverse cellular processes such as cell cycle regulation, circadian rhythms, apoptosis, transformation and tumorigenesis. In addition, there is increasing evidence...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2005.07.008
更新日期:2006-03-01 00:00:00
abstract::Epac1 is a cAMP-stimulated guanine exchange factor that activates Rap1. The protein product of the T cell leukemia 1 (TCL1) proto-oncogene binds to Akt enhancing its kinase activity. TCL1 and Epac promote cellular proliferation because of their activating effects on Akt. Employing macrophages, we have studied the mech...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2007.10.008
更新日期:2008-01-01 00:00:00
abstract::The protein kinase C (PKC) family is the most prominent target of tumor-promoting phorbol esters. For the PKCepsilon isozyme, different intracellular localizations and oncogenic potential in several but not all experimental systems have been reported. To obtain information about PKCepsilon-signaling, we investigated t...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.01.017
更新日期:2009-05-01 00:00:00
abstract::Na(+)/H(+) exchanger-1 (NHE-1) activity is known to play a critical role in the neuronal injury caused by glutamate. However, the underlying mechanism is not clear. This study shows that NHE-1 activation and its phosphorylation during glutamate exposure were attenuated by the inhibition of protein kinase C (PKC)-βI an...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.12.011
更新日期:2014-04-01 00:00:00
abstract::Circulating symmetric dimethylarginine (SDMA) is increased in patients with chronic kidney disease. SDMA is considered an inert metabolite, but because it can transported into cells, we studied the effect of SDMA on glomerular endothelial cells. SDMA suppressed VEGF-induced endothelial nitric oxide synthase (eNOS) pho...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.09.024
更新日期:2015-01-01 00:00:00
abstract::When oxygen sensing cells are excited by hypoxia, background K+ currents are inhibited. TASK-1, which is commonly expressed in oxygen sensing cells and makes a background K+ current, is inactivated by hypoxia. Thus TASK-1 is a candidate molecule responsible for hypoxic excitation. However, TASK-1 per se cannot sense o...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.05.025
更新日期:2006-04-01 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::Binding of urokinase-type plasminogen activator (uPA) to its receptor, uPAR, in estrogen receptor-α (ERα) expressing breast cancer cells, transiently activates ERK downstream of FAK, Src family kinases, and H-Ras. Herein, we show that when uPAR is over-expressed, in two separate ERα-positive breast cancer cell lines, ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.05.011
更新日期:2012-09-01 00:00:00
abstract::Sphingolipids and their synthetic enzymes have emerged as critical mediators in numerous diseases including inflammation, aging, and cancer. One enzyme in particular, sphingosine kinase (SK) and its product sphingosine-1-phosphate (S1P), has been extensively implicated in these processes. SK catalyzes the phosphorylat...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109875
更新日期:2021-03-01 00:00:00
abstract::Single disseminated tumor cells (DTC) can be detected in the bone marrow (BM) from 20% to 60% of patients with various tumors including non-small cell lung cancer (NSCLC). Detection of DTC in the BM of NSCLC patients is associated with poor prognosis and may be responsible for metastatic relapse. However, the function...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.07.003
更新日期:2011-12-01 00:00:00
abstract::Treatment of lucerne suspension culture cells with glycoprotein elicitor from the phytopathogenic fungus Verticillium albo-atrum R & B triggers Ca(2+)-mediated induction of antimicrobial secondary metabolites termed phytoalexins. The present study investigated the possible role of polyphosphoinositide signal transduct...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(93)90026-i
更新日期:1993-05-01 00:00:00
abstract::The possible involvement of zeta isozyme of protein kinase C (PKC zeta) in phorbol ester-induced signal transduction was investigated in mouse epidermal cells. Western blot analysis of RESOURCE Q column chromatography eluates obtained from 105,000 g supernatants and particulate fractions of epidermal cells was perform...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(95)00019-l
更新日期:1995-07-01 00:00:00
abstract::Peritoneal dialysis (PD) is a renal replacement therapy for patients with end-stage renal disease that is equivalent to hemodialysis with respect to adequacy, mortality, and other outcome parameters, yet providing superior quality-of-life measures and cost savings. However, long-term usage of the patient's peritoneal ...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2020.109778
更新日期:2020-11-01 00:00:00
abstract::Glucuronyl C5-epimerase (Hsepi) catalyzes the conversion of glucuronic acid to iduronic acid in the process of heparan sulfate biosynthesis. Targeted interruption of the gene, Glce, in mice resulted in neonatal lethality with varied defects in organ development. To understand the underlying molecular mechanisms of the...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.11.010
更新日期:2019-02-01 00:00:00
abstract::The kidney is one of the fastest-aging organs, and renal senescence has become a major disease affecting human health. Renal cellular senescence is regulated by the joint action of multiple signal transduction pathways. The previous study by our research group found that the Janus kinase 2 (JAK2)/signal transducer and...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.10.021
更新日期:2019-01-01 00:00:00
abstract::CCN1/CYR61 is a matricellular protein of the CCN family, comprising six secreted proteins specifically associated with the extracellular matrix (ECM). CCN1 acts as an enhancer of the cutaneous wound healing process by preventing hypertrophic scar formation through induction of myofibroblast senescence. In liver fibros...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.10.013
更新日期:2016-01-01 00:00:00
abstract::Cellular signal transmission requires the dynamic formation of spatiotemporally controlled molecular interactions. At the cell surface information is received by receptor complexes and relayed through intracellular signaling platforms which organize the actions of functionally interacting signaling enzymes and substra...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2017.05.012
更新日期:2017-09-01 00:00:00
abstract::Ephedrine (Eph) is one of alkaloids that has been isolated from the ancient herb ephedra (ma huang) and is used as the treatment of asthma, hypotension and fatigue. However, its molecular mechanism remains unknown. Thioredoxin-1 (Trx-1) is a redox regulating protein, which has various biological activities, including ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.02.007
更新日期:2013-05-01 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