ArticleMolecules (Basel, Switzerland)2016
Estrogen Receptor Signaling and the PI3K/Akt Pathway Are Involved in Betulinic Acid-Induced eNOS Activation.
Article in Molecules (Basel, Switzerland), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Paracrine Signaling in Cell-Biomaterial Interactions in Scaffold Vascularization: A Mini Review.Biomimetics (Basel, Switzerland) · 2026Review
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- The role of phosphoinositide 3-kinases in immune-inflammatory responses: potential therapeutic targets for abdominal aortic aneurysm.Cell cycle (Georgetown, Tex.) · 2022Review
- Regional Diversities in Fibrogenesis Weighed as a Key Determinant for Atrial Arrhythmogenesis.Biomedicines · 2021Review
- Bidirectional differentiation of BMSCs induced by a biomimetic procallus based on a gelatin-reduced graphene oxide reinforced hydrogel for rapid bone regeneration.Bioactive materials · 2021Article
- Estrogen activates endothelial exocytosis.Biochemical and biophysical research communications · 2021Article
- Signalling mechanisms in the cardiovascular protective effects of estrogen: With a focus on rapid/membrane signalling.Current research in physiology · 2021Review
- Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy.International journal of molecular sciences · 2020Review
- Betulinic Acid Inhibits Endometriosis Through Suppression of Estrogen Receptor β Signaling Pathway.Frontiers in endocrinology · 2020Article
- The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell Migration in Choroid-Retina Endothelial Cells.International journal of molecular sciences · 2019Article
- Comparison of diabetic nephropathy between male and female eNOSAmerican journal of physiology. Renal physiology · 2019Article
- Betulinic acid‑induced expression of nicotinamide adenine dinucleotide phosphate‑diaphorase in the immune organs of mice: A possible role of nitric oxide in immunomodulation.Molecular medicine reports · 2018Article
- Sex differences in pulmonary vascular control: focus on the nitric oxide pathway.Physiological reports · 2017Article
- Research Progress on Signaling Pathway-Associated Oxidative Stress in Endothelial Cells.Oxidative medicine and cellular longevity · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid with anti-inflammatory, antiviral and anti-cancer properties. Beneficial cardiovascular effects such as increased nitric oxide (NO) production through enhancement of endothelial NO synthase (eNOS) activity and upregulation of eNOS expression have been demonstrated for this compound. In the present study, immortalized human EA.hy 926 endothelial cells were incubated for up to 1 h with 1-100 µM BA and with the phosphatidylinositol-3-kinase (PI3K) inhibitors LY294002 and wortmannin, or the estrogen receptor (ER) antagonist ICI 182,780. Phosphorylation status of eNOS and total eNOS protein were analyzed by Western blotting using a serine 1177 phosphosite-specific antibody. Bioactive NO production was assessed by determination of cGMP content in rat lung fibroblasts (RFL-6) reporter cells. Short-term incubation of EA.hy 926 cells with BA resulted in eNOS phosphorylation at the serine 1177 residue in a concentration- and time-dependent manner with a half-maximal effective concentration of 0.57 µM. This was associated with an enhanced production of NO. BA-induced eNOS phosphorylation and NO production was completely blocked by pretreatment with ICI 182,780, and was attenuated by pretreatment with the PI3K inhibitors wortmannin and LY294002. These results indicate that fast non-genomic effects of ER with downstream signaling through the PI3K/Akt pathway and consecutive eNOS phosphorylation at serine 1177 are involved in BA-induced eNOS activation.
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