Faculty Opinions recommendation of A complex signaling pathway regulates SRp38 phosphorylation and pre-mRNA splicing in response to heat shock.

2007 ◽  
Author(s):  
Reinhard Lührmann
Keyword(s):  
Heat Shock ◽  
Signaling Pathway ◽  
Mrna Splicing ◽  
Complex Signaling

scholarly journals Neuraminidase activity mediates IL-6 production by activated lupus-prone mesangial cells

2018 ◽  
Vol 314 (4) ◽  
pp. F630-F642 ◽  
Author(s):  
Kamala Sundararaj ◽  
Jessalyn I. Rodgers ◽  
Subathra Marimuthu ◽  
Leah J. Siskind ◽  
Evelyn Bruner ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Signaling Pathway ◽  
Mesangial Cells ◽  
Morbidity And Mortality ◽  
Receptor Complex ◽  
Catabolic Pathway ◽  
Neuraminidase Activity ◽  
Complex Signaling

The development of nephritis is a leading cause of morbidity and mortality in lupus patients. Although the general pathophysiological progression of lupus nephritis is known, the molecular mediators and mechanisms are incompletely understood. Previously, we demonstrated that the glycosphingolipid (GSL) catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human lupus patients with nephritis. Specifically, the activity of neuraminidase (NEU) and expression of Neu1, an enzyme in the GSL catabolic pathway is significantly increased. To better understand the role and mechanisms by which this pathway contributes to the progression of LN, we analyzed the expression and effects of NEU activity on the function of MRL/lpr lupus-prone mesangial cells (MCs). We demonstrate that NEU1 and NEU3 promote IL-6 production in MES13 MCs. Neu1 expression, NEU activity, and IL-6 production are significantly increased in stimulated primary MRL/lpr lupus-prone MCs, and blocking NEU activity inhibits IL-6 production. NEU1 and NEU3 expression overlaps IgG deposits in MCs in vitro and in renal sections from nephritic MRL/lpr mice. Together, our results suggest that NEU activity mediates IL-6 production in lupus-prone MCs possibly through an IgG-receptor complex signaling pathway.

scholarly journals NF-κB mediates lipopolysaccharide-induced alternative pre-mRNA splicing of MyD88 in mouse macrophages

2020 ◽  
Vol 295 (18) ◽  
pp. 6236-6248
Author(s):  
Frank Fang-Yao Lee ◽  
Kevin Davidson ◽  
Chelsea Harris ◽  
Jazalle McClendon ◽  
William J. Janssen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Mrna Splicing ◽  
Dominant Negative ◽  
Mrna Isoforms ◽  
Inflammatory Signaling ◽  
Tlr Signaling ◽  
Tlr4 Agonist ◽  
Alternatively Spliced ◽  
Tlr Signaling Pathway

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.

scholarly journals NF-κB signaling pathway is inhibited by heat shock independently of active transcription factor HSF1 and increased levels of inducible heat shock proteins

2011 ◽  
Vol 16 (12) ◽  
pp. 1168-1175 ◽  
Author(s):  
Patryk Janus ◽  
Małgorzata Pakuła-Cis ◽  
Magdalena Kalinowska-Herok ◽  
Natalia Kashchak ◽  
Katarzyna Szołtysek ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Signaling Pathway ◽  
Active Transcription ◽  
Shock Proteins

Heat shock protein 72 inhibits c-Jun N-terminal kinase 3 signaling pathway via Akt1 during cerebral ischemia

2012 ◽  
Vol 317 (1-2) ◽  
pp. 123-129 ◽  
Author(s):  
Dashi Qi ◽  
Hongzhi Liu ◽  
Jian Niu ◽  
Xing Fan ◽  
Xiangru Wen ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Signaling Pathway ◽  
Heat Shock Protein 72

scholarly journals The Novel Peptide AEDPPE Alleviates Trophoblast Cell Dysfunction Associated With Preeclampsia by Regulating the NF-κB Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Yixiao Wang ◽  
Yan Cao ◽  
Xiaohong Ji ◽  
Ting Li ◽  
Lu Xue ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Signaling Pathway ◽  
Rat Model ◽  
Biological Effects ◽  
Cytokine Expression ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
Tnf Α

Background: Preeclampsia (PE) is a serious risk to the health of pregnant women and fetuses during pregnancy, and there is no effective treatment for this condition. Although many reports have confirmed the therapeutic effects of peptides in diseases, the role of peptides in PE remains poorly understood.Methods: A differentially expressed peptide in PE (AEDPPE) is derived from heat-shock protein beta-1 (HSPB1), amino acids 100 to 109 (DVNHFAPDEL), which we identified in a previous study. We synthesized AEDPPE and investigated its effect on HTR-8/SVneo cell function using a Cell Counting Kit-8, flow cytometric assay, and Transwell and wound-healing assays. Quantitative reverse transcription-PCR and ELISA were used to determine cytokine expression. Pull-down assay, mass spectrometry, Western blot analysis, and immunofluorescence were used to explore the potential targets and signaling pathways regulated by AEDPPE. Finally, we assessed the effect of AEDPPE in the lipopolysaccharide (LPS)-induced PE-like rat model.Results: AEDPPE significantly promoted the migration and invasion of HTR-8/SVneo cells, and it decreased the expression of interleukins 1 beta (IL-1β), interleukin 6 (IL-6), and interleukin 8 (IL-8). These functions performed by AEDPPE remained evident after injury to HTR-8/SVneo cells with tumor necrosis factor-alpha (TNF-α), and AEDPPE reversed the elevated sFlt-1/PlGF ratio induced by TNF-α. AEDPPE may exert these biological effects by binding to heat-shock protein 90β (HSP 90β) and, thus, affect the NF-κB signaling pathway. In an LPS-induced PE-like rat model, AEDPPE significantly improved PE symptoms and fetal rat outcomes.Conclusion: Our study showed that AEDPPE enhanced trophoblast migration and invasion and reduced inflammatory cytokine expression, and we hypothesized that these actions involved the NF-κB signaling pathway. The use of AEDPPE may thus develop into a novel modality in the treatment of PE.

Patterning of dopaminergic neurotransmitter identity among Caenorhabditis elegans ray sensory neurons by a TGFbeta family signaling pathway and a Hox gene

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5819-5831 ◽  
Author(s):  
R. Lints ◽  
S.W. Emmons
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Sensory Neurons ◽  
Ectopic Expression ◽  
Temperature Shift ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Hox Gene

We have investigated the mechanism that patterns dopamine expression among Caenorhabditis elegans male ray sensory neurons. Dopamine is expressed by the A-type sensory neurons in three out of the nine pairs of rays. We used expression of a tyrosine hydroxylase reporter transgene as well as direct assays for dopamine to study the genetic requirements for adoption of the dopaminergic cell fate. In loss-of-function mutants affecting a TGFbeta family signaling pathway, the DBL-1 pathway, dopaminergic identity is adopted irregularly by a wider subset of the rays. Ectopic expression of the pathway ligand, DBL-1, from a heat-shock-driven transgene results in adoption of dopaminergic identity by rays 3–9; rays 1 and 2 are refractory. The rays are therefore prepatterned with respect to their competence to be induced by a DBL-1 pathway signal. Temperature-shift experiments with a temperature-sensitive type II receptor mutant, as well as heat-shock induction experiments, show that the DBL-1 pathway acts during an interval that extends from two to one cell generation before ray neurons are born and begin to differentiate. In a mutant of the AbdominalB class Hox gene egl-5, rays that normally express EGL-5 do not adopt dopaminergic fate and cannot be induced to express DA when DBL-1 is provided by a heat-shock-driven dbl-1 transgene. Therefore, egl-5 is required for making a subset of rays capable of adopting dopaminergic identity, while the function of the DBL-1 pathway signal is to pattern the realization of this capability.

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