Arachidonic Acid-Dependent Pathway Inhibition in Platelets: its Role in Multiple Injury-Induced Coagulopathy and the Potential Mechanisms

Shock ◽  
2020 ◽  
Vol 55 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Yao Tang ◽  
Sunhua Huang ◽  
Wenhao Lin ◽  
Ke Wen ◽  
Zhexuan Lin ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Multiple Injury ◽  
Pathway Inhibition ◽  
Dependent Pathway

Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway

2013 ◽  
Vol 304 (1) ◽  
pp. C56-C67 ◽  
Author(s):  
James F. Markworth ◽  
David Cameron-Smith
Keyword(s):  
Skeletal Muscle ◽  
Arachidonic Acid ◽  
Cell Growth ◽  
Muscle Cell ◽  
Myogenic Differentiation ◽  
Skeletal Muscle Cell ◽  
Diverse Range ◽  
Cox 2 ◽  
Dependent Pathway

Arachidonic acid (AA) is the metabolic precursor to a diverse range of downstream bioactive lipid mediators. A positive or negative influence of individual eicosanoid species [e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro . C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was amplified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AA-stimulated growth was associated with markedly increased secretion of PGF2α and PGE2; however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway.

scholarly journals P034 Human primary 2D culture as a tool to explore JAK1 pathway inhibition in the intestinal epithelium using siRNA technology

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S147-S148
Author(s):  
I Dotti ◽  
E Sulpice ◽  
A Nougarède ◽  
D Jary ◽  
F Clément ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Target Genes ◽  
Local Therapy ◽  
The Novel ◽  
Sirna Transfection ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Pathway Inhibition ◽  
Human Intestinal Epithelium ◽  
Dependent Pathway

Abstract Background Oral inhibitors of JAK1 have become promising therapeutic agents for the treatment of inflammatory bowel diseases (IBD); however, concerns have been raised regarding their specificity and safety profiles. Currently, a local therapy based on specific JAK1 siRNA combined with lipid nanoparticle (LNP) technology is under investigation as a safer alternative to JAK inhibitors.The purpose of this study is to explore the inhibition of the JAK1 pathway in the intestinal epithelium mediated by siRNA/LNP technology, using human primary 2D culture. Methods Human primary 2D cultures were generated from colonic 3D organoids of non-IBD donors. The efficiency of JAK1 pathway inhibition was tested in IFN-y stimulated cultures using either filgotinib (a JAK1 inhibitor, used as a control) or the novel human JAK1 siRNA. JAK1 siRNA transfection was performed using Lipofectamine or LNPs. qPCR was performed on a panel of JAK1 target genes to evaluate the efficiency of JAK1 pathway inhibition. Results Incubation of the 2D culture with IFN-y induced the activation of the JAK1 pathway, as suggested by the significant up-regulation of JAK1-dependent genes (i.e., CXCL10, SOCS1, SOCS3 and PLA2G2A). The addition of filgotinib to the culture efficiently inhibited the JAK1 pathway by suppressing the expression of JAK1-target genes. JAK1 siRNA transfection using Lipofectamine reduced JAK1 mRNA expression by 50%, which was mirrored by the concomitant down-regulation (between 60 and 80%) of JAK1-dependent genes. Importantly, the silencing efficiency of the JAK1-dependent pathway by LNPs was comparable to that observed using Lipofectamine. Conclusion Organoid-derived 2D culture is a useful model for investigating the activation of the JAK1 pathway and its pharmacological inhibition in human intestinal epithelium. In particular, siRNA/LNP nanoplexes may be a promising technology for locally delivering highly specific siRNAs to the intestinal mucosa, which could pave the way for the development of more effective treatments for IBD patients.

scholarly journals Integrin-dependent homotypic adhesion of neutrophils. Arachidonic acid activates Raf-1/Mek/Erk via a 5-lipoxygenase- dependent pathway.

1998 ◽  
Vol 102 (1) ◽  
pp. 165-175 ◽  
Author(s):  
C Capodici ◽  
M H Pillinger ◽  
G Han ◽  
M R Philips ◽  
G Weissmann
Keyword(s):  
Arachidonic Acid ◽  
Dependent Pathway ◽  
Homotypic Adhesion

Oleic acid promotes migration on MDA-MB-231 breast cancer cells through an arachidonic acid-dependent pathway

2010 ◽  
Vol 42 (2) ◽  
pp. 306-317 ◽  
Author(s):  
Napoleon Navarro-Tito ◽  
Adriana Soto-Guzman ◽  
Luis Castro-Sanchez ◽  
Raul Martinez-Orozco ◽  
Eduardo Perez Salazar
Keyword(s):  
Breast Cancer ◽  
Arachidonic Acid ◽  
Oleic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Dependent Pathway

Angiotensin II activates Akt/protein kinase B by an arachidonic acid/redox‐dependent pathway and independent of phosphoinositide 3‐kinase

2001 ◽  
Vol 15 (11) ◽  
pp. 1909-1920 ◽  
Author(s):  
Yves Gorin ◽  
Nam‐Ho Kim ◽  
Denis Feliers ◽  
Basant Bhandari ◽  
Goutam Ghosh Choudhury ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Phosphoinositide 3 Kinase ◽  
Dependent Pathway

scholarly journals Arachidonic acid inhibits the production of angiotensin-converting enzyme in human primary adipocytes via a NF-κB-dependent pathway

2020 ◽  
Vol 8 (24) ◽  
pp. 1652-1652
Author(s):  
Li Xu ◽  
Rita Schüler ◽  
Chenchen Xu ◽  
Nicole Seebeck ◽  
Mariya Markova ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Dependent Pathway
Sign in / Sign up

Export Citation Format

Share Document