Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells (RGCs) in a rat chronic ocular hypertension (COH) model. Here, we investigated the expression of endothelin-1 (ET-1), a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure (IOP) was induced in the right eye of SD rats using argon laser photocoagulation. (1) The expression of ET-1, ETA and ETB in normal and COH retinas was studied. (2) Some COH rats were fed daily with Lycium barbarum Polysaccharides (LBP) using 1 mg/kg or phosphate-buffered saline (PBS) for 3 weeks (started 1 week before photocoagulation). The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that (1) Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. (2) After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. (3) By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.
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http://dx.doi.org/10.3969/j.issn.1673-5374.2012.09.001 | DOI Listing |
Eur J Pharmacol
December 2024
Department of Physiology, School of Medicine, University of Valencia, Spain; Institute of Health Research INCLIVA, Valencia, Spain; Center for Biomedical Research Network on Cardiovascular Diseases (CIBER-CV), Madrid, Spain. Electronic address:
Sympathetic nervous system (SNS), endothelin 1 (ET-1) and angiotensin II (Ang II) are involved in the pathophysiology of acute myocardial infarction (AMI). Valproic acid (VPA) is under study for the treatment against AMI due to its beneficial cardiac effects. However, the vascular effects of VPA on the activation of the SNS, ET-1 and Ang II after AMI are not fully studied.
View Article and Find Full Text PDFFront Pharmacol
November 2024
Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gaithersburg, MD, United States.
Introduction: Endothelin-1 (ET-1) regulates renal and vascular function, but the clinical utility of selective ET receptor antagonists has been limited due to associated fluid retention. The mechanisms underlying fluid retention remain poorly understood but could be a consequence of changes in ET-1 binding to the unantagonized ET receptor, either through increased ET-1 or non-selective ET.
Methods: A mathematical model of ET-1 kinetics was developed to quantify effects of ET antagonist exposure and selectivity on concentrations of ET-1 and its complexes with ET and ET receptors.
Am J Infect Control
November 2024
Department of Infectious Diseases, Medical Mycology Research Center, Chiba University, Chiba-city, Chiba, Japan.
Foods
October 2024
Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, İstanbul University-Cerrahpaşa, İstanbul 34320, Türkiye.
Biosci Rep
December 2024
Preclinical Models and New Therapeutic Agents Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Regina Elena National Cancer Institute, Rome, Italy.
The high-grade serous ovarian cancer (HG-SOC) is a notoriously challenging disease, characterized by a rapid peritoneal dissemination. HG-SOC cells leverage actin-rich membrane protrusions, known as invadopodia, to degrade the surrounding extracellular matrix (ECM) and invade, initiating the metastatic cascade. In HG-SOC, the endothelin-1 (ET-1)/endothelin A receptor (ETAR)-driven signaling coordinates invadopodia activity, however how this axis integrates pro-oncogenic signaling routes, as YAP-driven one, impacting on the invadopodia-mediated ECM degradation and metastatic progression, deserves a deeper investigation.
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