Search results for "PROTEIN KINASES"
showing 10 items of 427 documents
Post-Transcriptional Regulation of Human Inducible Nitric-Oxide Synthase Expression by the Jun N-terminal Kinase
2007
Human inducible nitric-oxide synthase (iNOS) expression is regulated both at transcriptional and post-transcriptional levels. In the present study, the effect of Jun N-terminal kinase (JNK) on human iNOS expression was investigated. In A549/8 human alveolar epithelial cells, both the inhibition of JNK by a pharmacological inhibitor anthra[1,9-cd]pyrazol-6(2H)-one1,9-pyrazoloanthrone (SP600125) and small interfering RNA (siRNA)-mediated down-regulation of JNK led to a reduction of iNOS mRNA and protein expression. iNOS promoter activity was not affected by these treatments. Hence, JNK seems to regulate iNOS expression through post-transcriptional mechanisms by stabilizing iNOS mRNA. Our labo…
Response of yeast cells to high glucose involves molecular and physiological differences when compared to other osmostress conditions.
2015
Yeast cells can be affected by several causes of osmotic stress, such as high salt, sorbitol or glucose concentrations. The last condition is particularly interesting during natural processes where this microorganism participates. Response to osmostress requires the HOG (High Osmolarity Glycerol) pathway and several transcription factors, including Hot1, which plays a key role in high glucose concentrations. In this work, we describe how the yeast response to osmotic stress shows differences in accordance with the stress agent responsible for it. Compared with other conditions, under high glucose stress, delocalization of MAPK (Mitogen-Activated Protein Kinase) Hog1 is slower, induction of …
Molecular mechanisms of sorafenib action in liver cancer cells.
2012
Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced hepatocellular carcinoma (HCC). However, as the clinical application of sorafenib evolves, there is increasing interest in defining the mechanisms underlying its anti-tumor activity. Considering that this specific inhibitor could target unexpected molecules depending on the biologic context, a precise understanding of its mechanism of action could be critical to maximize its treatment efficacy, while minimizing adverse effects. Two human HCC cell lines (HepG2 and Huh7), carrying different biological and genetic characteristics, were used in this study to examine the intracellular events leading …
p38 MAPK activation is required for Paracentrotus lividus skeletogenesis
2008
We investigated the p38 MAPK role during sea urchin, Paracentrotus lividus, development. We found that at the morula stage, before the onset of skeletogenesis, p38 MAPK shows a peak of activity, and we tested whether p38 MAPK activity has any effect on skeletogenesis. By immunohistochemistry on whole-mount embryos we show the preferential localization of the active p38 form both in the presumptive PMCs and bilateral spiculo- genesis centers in control embryos, and in the radialized supernumerary spiculogenesis centers induced by NiCl2 treatment. By using SB203580, a p38 MAPK specific inhibitor, we show that p38 activity is required both for the initial triradiate spicule rudiments formation…
Oleuropein protects against dextran sodium sulfate-induced chronic colitis in mice.
2013
The anti-inflammatory effect of oleuropein (1), the major phenolic secoiridoid in Olea europaea, was evaluated in an experimental model of chronic colitis in mice. Animals were exposed to four repeated cycles of dextran sodium sulfate in drinking water followed by a 7-day rest period. Animals receiving a standard diet supplemented with 0.25% of 1 (equivalent to 500 mg/kg/day) for 56 days exhibited a decrease of inflammatory symptoms, as reflected by improvement of disease activity index and histopathological changes. It was found that 1 decreased inflammatory cell recruitment and the release of inflammatory cytokines interleukin (IL)-1β and IL-6 with increased IL-10 levels in colon tissue. …
Hematopoietic stem cell quiescence and function are controlled by the CYLD–TRAF2–p38MAPK pathway
2015
Tesio at al. identify a novel pathway controlled by the tumor suppressor and deubiquitinase cylindromatosis (CYLD), which is involved in the regulation of hematopoietic stem cell quiescence and repopulation potential.
Serine- and Threonine/Valine-Dependent Activation of PDK and Tor Orthologs Converge on Sch9 to Promote Aging
2014
Dietary restriction extends longevity in organisms ranging from bacteria to mice and protects primates from a variety of diseases, but the contribution of each dietary component to aging is poorly understood. Here we demonstrate that glucose and specific amino acids promote stress sensitization and aging through the differential activation of the Ras/cAMP/PKA, PKH1/2 and Tor/S6K pathways. Whereas glucose sensitized cells through a Ras-dependent mechanism, threonine and valine promoted cellular sensitization and aging primarily by activating the Tor/S6K pathway and serine promoted sensitization via PDK1 orthologs Pkh1/2. Serine, threonine and valine activated a signaling network in which Sch…
JNK phosphorylation relieves HDAC3-dependent suppression of the transcriptional activity of c-Jun
2003
The AP-1 transcription factor c-Jun is a prototypical nuclear effector of the JNK signal transduction pathway. The integrity of JNK phosphorylation sites at serines 63/73 and at threonines 91/93 in c-Jun is essential for signal-dependent target gene activation. We show that c-Jun phosphorylation mediates dissociation of an inhibitory complex, which is associated with histone deacetylase 3 (HDAC3). The subsequent events that ultimately cause increased mRNA synthesis are independent of c-Jun phosphorylation and its interaction with JNK. These findings provide an 'activation by de-repression' model as an explanation for the stimulatory function of JNK on c-Jun.
Ras, Rap, and Rac Small GTP-binding Proteins Are Targets for Clostridium sordellii Lethal Toxin Glucosylation
1996
Lethal toxin (LT) from Clostridium sordellii is one of the high molecular mass clostridial cytotoxins. On cultured cells, it causes a rounding of cell bodies and a disruption of actin stress fibers. We demonstrate that LT is a glucosyltransferase that uses UDP-Glc as a cofactor to covalently modify 21-kDa proteins both in vitro and in vivo. LT glucosylates Ras, Rap, and Rac. In Ras, threonine at position 35 was identified as the target amino acid glucosylated by LT. Other related members of the Ras GTPase superfamily, including RhoA, Cdc42, and Rab6, were not modified by LT. Incubation of serum-starved Swiss 3T3 cells with LT prevents the epidermal growth factor-induced phosphorylation of m…
pRb suppresses camptothecin-induced apoptosis in human osteosarcoma Saos-2 cells by inhibiting c-Jun N-terminal kinase
2001
AbstractThis paper studies the cytotoxic effect induced by the topoisomerase I inhibitor camptothecin in human osteosarcoma Saos-2 cells, which lack p53 and contain a non-functional form of the product of the retinoblastoma gene, pRb. Cytotoxicity induced by camptothecin was dose- and time-dependent; the treatment with 100 nM camptothecin reduced cell viability by 50% at 32 h and by 75% at 72 h of exposure. The cytotoxic effect was caused by apoptosis, as ascertained by morphological evidence, acridine orange-ethidium bromide staining and flow cytometric analysis. Apoptosis was accompanied by both the activation of caspase-3 and the fragmentation of poly(ADP-ribose) polymerase. Treatment wi…