scholarly journals Mathematical Modeling and Parameter Estimation of Intracellular Signaling Pathway: Application to LPS-induced NFκB Activation and TNFα Production in Macrophages

Processes ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 21 ◽  
Author(s):  
Dongheon Lee ◽  
Yufang Ding ◽  
Arul Jayaraman ◽  
Joseph Kwon
Keyword(s):  
Mathematical Modeling ◽  
Parameter Estimation ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Intracellular Signaling Pathway

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 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

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

Aldosterone inhibits apical NHE3 and HCO3− absorption via a nongenomic ERK-dependent pathway in medullary thick ascending limb

2006 ◽  
Vol 291 (5) ◽  
pp. F1005-F1013 ◽  
Author(s):  
Bruns A. Watts ◽  
Thampi George ◽  
David W. Good
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Thick Ascending Limb ◽  
Erk Activation ◽  
Intracellular Signaling Pathway ◽  
Cellular Processes ◽  
Medullary Thick Ascending Limb ◽  
Erk Activity ◽  
Rapid Activation

Although aldosterone influences a variety of cellular processes through nongenomic mechanisms, the significance of nongenomic pathways for aldosterone-induced regulation of epithelial function is not understood. Recently, we demonstrated that aldosterone inhibits transepithelial HCO3− absorption in the medullary thick ascending limb (MTAL) through a nongenomic pathway. This inhibition is mediated through a direct cellular action of aldosterone to inhibit the apical membrane NHE3 Na+/H+ exchanger. The present study was designed to identify the intracellular signaling pathway(s) responsible for this aldosterone-induced transport regulation. In rat MTALs perfused in vitro, addition of 1 nM aldosterone to the bath decreased HCO3− absorption by 30%. This inhibition was not mediated by cAMP/PKA and was not prevented by inhibitors of PKC or PI3-K, pertussis toxin, or rapamycin. The inhibition of HCO3− absorption by aldosterone was largely eliminated by the MEK/ERK inhibitors U-0126 and PD-98059. Aldosterone increased ERK activity 1.8-fold in microdissected MTALs. This ERK activation is rapid (≤5 min) and is blocked by U-0126 or PD-98059 but is unaffected by spironolactone or actinomycin D. Pretreatment with U-0126 to block ERK activation prevented the effect of aldosterone to inhibit apical NHE3. These data demonstrate that aldosterone inhibits NHE3 and HCO3− absorption in the MTAL through rapid activation of the ERK signaling pathway. The results identify NHE3 as a target for nongenomic regulation by aldosterone and establish a role for ERK in the acute regulation of NHE3 and its epithelial absorptive functions.

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