scholarly journals Intracellular Signaling Pathway Activation via TGF-β Differs in the Anterior and Posterior Axis During Palatal Development

2016 ◽  
Vol 25 (2) ◽  
pp. 195-204
Author(s):  
Arisa Higa ◽  
Kyoko Oka ◽  
Michiko Kira-Tatsuoka ◽  
Shougo Tamura ◽  
Satoshi Itaya ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Intracellular Signaling Pathway ◽  
Pathway Activation ◽  
Palatal Development

Role of NO in endothelin-regulated drug transport in the renal proximal tubule

2002 ◽  
Vol 282 (3) ◽  
pp. F458-F464 ◽  
Author(s):  
Sylvia Notenboom ◽  
David S. Miller ◽  
Paul Smits ◽  
Frans G. M. Russel ◽  
Rosalinde Masereeuw
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Drug Transport ◽  
No Production ◽  
No Donor ◽  
Intracellular Signaling Pathway ◽  
Pathway Activation ◽  
Quantitative Image ◽  
The Status ◽  
Synthase Inhibitor

We previously demonstrated in intact killifish renal proximal tubules that endothelin (ET), acting through an ETB receptor and protein kinase C (PKC), reduced transport mediated by multidrug resistance-associated protein 2 (Mrp2), i.e., luminal accumulation of fluorescein methotrexate (FL-MTX) (Masereeuw R, Terlouw SA, Van Aubel RAMH, Russel FGM, and Miller DS. Mol Pharmacol 57: 59–67, 2000). In the present study, we used confocal microscopy and quantitative image analysis to measure Mrp2-mediated transport of FL-MTX in killifish tubules as an indicator of the status of this ET-fired, intracellular signaling pathway. Exposing tubules to sodium nitroprusside (SNP), a nitric oxide (NO) donor, signaled a reduction in luminal accumulation of FL-MTX, which suggested pathway activation. N G-monomethyl-l-arginine (l-NMMA), an NO synthase inhibitor, blocked the action of ET-1 on transport. Because SNP effects on transport were blocked by bisindoylmaleide, a PKC-selective inhibitor, but not by RES-701–1, an ETB-receptor antagonist, generation of NO occurred after ETB receptor signaling but before PKC activation. NO generation was implicated in the actions of several nephrotoxicants, i.e., diatrizoate, gentamicin, amikacin, HgCl2, and CdCl2, each of which decreased Mrp2-mediated transport by activating ET signaling. For each nephrotoxicant, decreased FL-MTX transport was prevented when tubules were exposed tol-NMMA. ET-1 and each nephrotoxicant stimulated NO production by the tubules, as determined by a fluorescence-based assay. Together, the data show that NO generation follows ET binding to the basolateral ETB receptor and that, in activating the ET-signaling pathway, nephrotoxicants produce NO, a molecule that could contribute to subsequent toxic effects.

scholarly journals Oncofinder, a new method for the analysis of intracellular signaling pathway activation using transcriptomic data

2014 ◽  
Vol 5 ◽  
Author(s):  
Anton A. Buzdin ◽  
Alex A. Zhavoronkov ◽  
Mikhail B. Korzinkin ◽  
Larisa S. Venkova ◽  
Alexander A. Zenin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
New Method ◽  
Intracellular Signaling Pathway ◽  
Transcriptomic Data ◽  
Pathway Activation

scholarly journals Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain

2021 ◽  
Vol 17 ◽  
pp. 174480692110033
Author(s):  
Travis Okerman ◽  
Taylor Jurgenson ◽  
Madelyn Moore ◽  
Amanda H Klein
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Morphine Tolerance ◽  
Spinal Nerve ◽  
Intracellular Signaling Pathway ◽  
Spinal Cord Dorsal ◽  
Phosphoinositide 3 Kinase ◽  
Induced Tolerance

Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl/6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis of Pik3cg, Akt1, Pten, and nNos1. This pathway was downregulated in the spinal cord with increased expression in the sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We also observed a significant increase in phosphorylated- JNK levels in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance in the peripheral nervous system. Continued research into this pathway will contribute to the development of new analgesic drug therapies.

scholarly journals Insulin-stimulated GLUT4 Translocation Is Mediated by a Divergent Intracellular Signaling Pathway

1995 ◽  
Vol 270 (47) ◽  
pp. 27991-27994 ◽  
Author(s):  
Tetsuro Haruta ◽  
Aaron J. Morris ◽  
David W. Rose ◽  
James G. Nelson ◽  
Michael Mueckler ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Glut4 Translocation ◽  
Intracellular Signaling Pathway

scholarly journals Intracellular signaling pathway to prevent caspase activation in osteoclasts.

1999 ◽  
Vol 79 ◽  
pp. 278
Author(s):  
Mitsue Shibata ◽  
Kazuhiro Kanaoka ◽  
Yasuhiro Kobayashi ◽  
Yuzo Kato ◽  
Hideaki Sakai
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Caspase Activation ◽  
Intracellular Signaling Pathway

scholarly journals Mel1c Mediated Monochromatic Light-Stimulated IGF-I Synthesis through the Intracellular Gαq/PKC/ERK Signaling Pathway

2019 ◽  
Vol 20 (7) ◽  
pp. 1682
Author(s):  
Shujie Ning ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong ◽  
Yaoxing Chen
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Monochromatic Light ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Erk Signaling ◽  
Sham Operation ◽  
Intracellular Signaling Pathway ◽  
Igf I

Previous studies have demonstrated that monochromatic light affects plasma melatonin (MEL) levels, which in turn regulates hepatic insulin-like growth factor I (IGF-I) secretion via the Mel1c receptor. However, the intracellular signaling pathway initiated by Mel1c remains unclear. In this study, newly hatched broilers, including intact, sham operation, and pinealectomy groups, were exposed to either white (WL), red (RL), green (GL), or blue (BL) light for 14 days. Experiments in vivo showed that GL significantly promoted plasma MEL formation, which was accompanied by an increase in the MEL receptor, Mel1c, as well as phosphorylated extracellular regulated protein kinases (p-ERK1/2), and IGF-I expression in the liver, compared to the other light-treated groups. In contrast, this GL stimulation was attenuated by pinealectomy. Exogenous MEL elevated the hepatocellular IGF-I level, which is consistent with increases in cyclic adenosine monophosphate (cAMP), Gαq, phosphorylated protein kinase C (p-PKC), and p-ERK1/2 expression. However, the Mel1c selective antagonist prazosin suppressed the MEL-induced expression of IGF-I, Gαq, p-PKC, and p-ERK1/2, while the cAMP concentration was barely affected. In addition, pretreatment with Ym254890 (a Gαq inhibitor), Go9863 (a PKC inhibitor), and PD98059 (an ERK1/2 inhibitor) markedly attenuated MEL-stimulated IGF-I expression and p-ERK1/2 activity. These results indicate that Mel1c mediates monochromatic GL-stimulated IGF-I synthesis through intracellular Gαq/PKC/ERK signaling.

scholarly journals Akt Inhibitor Akt-IV Blocks Virus Replication through an Akt-Independent Mechanism

2009 ◽  
Vol 83 (22) ◽  
pp. 11665-11672 ◽  
Author(s):  
Ewan F. Dunn ◽  
Rachel Fearns ◽  
John H. Connor
Keyword(s):  
Signaling Pathway ◽  
Virus Replication ◽  
Intracellular Signaling ◽  
Akt Pathway ◽  
Akt Inhibitor ◽  
Antiviral Compound ◽  
Intracellular Signaling Pathway ◽  
Cytopathic Effects ◽  
Syncytial Virus

ABSTRACT Many viruses activate the phosphatidylinositol 3′-kinase (PI3k)/Akt intracellular signaling pathway to promote viral replication. We have analyzed whether a rapidly replicating rhabdovirus, vesicular stomatitis virus (VSV), requires the PI3k/Akt signaling pathway for its replication. Through the use of chemical inhibitors of PI3k and Akt, we show that VSV replication and cytopathic effects do not require activation of these kinases. Inhibitors that block the activating phosphorylations of Akt at threonine 308 (Thr308) and serine 473 (Ser473) did not inhibit VSV protein expression or the induction of the cytopathic effects of VSV. One compound, Akt inhibitor Akt-IV, inhibited the replication of VSV, respiratory syncytial virus, and vaccinia virus but increased the phosphorylation of Akt at positions Thr308 and Ser473 and did not inhibit Akt kinase activity in vitro. Together, our data suggest that the PI3k/Akt pathway is of limited relevance to the replication of VSV but that Akt inhibitor Akt-IV is a novel broad-spectrum antiviral compound with a mechanism differing from that of its previously reported effect on the PI3k/Akt pathway. Identification of other targets for this compound may define a new approach for blocking virus replication.

Regulation of alternative splicing of caspase-2 through an intracellular signaling pathway in response to pro-apoptotic stimuli

2005 ◽  
Vol 145 (2) ◽  
pp. 105-110 ◽  
Author(s):  
Nozomi Iwanaga ◽  
Makoto Kamachi ◽  
Kouichiro Aratake ◽  
Yasumori Izumi ◽  
Hiroaki Ida ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Intracellular Signaling Pathway ◽  
Caspase 2
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