ArticleFEBS open bio2021
Phosphorylation of Akt at Thr308 regulates p-eNOS Ser1177 during physiological conditions.
Article in FEBS open bio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
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- The Effects of a Novel Nutraceutical Composition Containing Coenzyme QFood science & nutrition · 2025Article
- MAPK, PI3K/Akt Pathways, and GSK-3β Activity in Severe Acute Heart Failure in Intensive Care Patients: An Updated Review.Journal of cardiovascular development and disease · 2025Review
- Angiogenic Events Positively Modulated by Complex Magnetic Fields in an In Vitro Endothelial Cell Model.Cells · 2025Article
- Endothelial cell-selective adhesion molecule deficiency exhibits increased pulmonary vascular resistance due to impaired endothelial nitric oxide signaling.American journal of physiology. Heart and circulatory physiology · 2025Article
- SIRT1: The first key to unlocking the mystery of cardiovascular diseases.Frontiers in pharmacology · 2025Review
- Sericin/polyvinyl alcohol hydrogel optimization for enhanced angiogenesis: a promising strategy for treating chronic osteomyelitis.PloS one · 2025Article
- Ginsenoside Rb1 prevents age-related endothelial senescence by modulating SIRT1/caveolin-1/enos signaling pathway.Heliyon · 2024Article
- Emerging and multifaceted potential contributions of polyphenols in the management of type 2 diabetes mellitus.World journal of diabetes · 2024Review
- The role of miR-134-5p in 7-ketocholesterol-induced human aortic endothelial dysfunction.EXCLI journal · 2024Article
- The evolving functions of the vasculature in regulating adipose tissue biology in health and obesity.Nature reviews. Endocrinology · 2023Review
- Aqueous Fraction fromNutrients · 2023Article
- iNOS contributes to heart failure with preserved ejection fraction through mitochondrial dysfunction and Akt S-nitrosylation.Journal of advanced research · 2023Article
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- Schisandrin B suppresses osteosarcoma lung metastasisOncology reports · 2022Article
- Extracellular cyclophilins A and C induce dysfunction of pancreatic microendothelial cells.Frontiers in physiology · 2022Article
- A comprehensive review of the novel therapeutic targets for the treatment of diabetic cardiomyopathy.Therapeutic advances in cardiovascular diseaseReview
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) plays a crucial role in maintaining vascular homeostasis. As a hallmark of eNOS activation, phosphorylation of eNOS at Ser1177 induced by activated protein kinase B (PKB/Akt) is pivotal for NO production. The complete activation of Akt requires its phosphorylation of both Thr308 and Ser473. However, which site plays the main role in regulating phosphorylation of eNOS Ser1177 is still controversial. The purpose of the present study is to explore the specific regulatory mechanism of phosphorylated Akt in eNOS activation. Inhibition of Akt Thr308 phosphorylation by a specific inhibitor or by siRNA in vitro led to a decrease in eNOS phosphorylation at Ser1177 and to lower NO concentration in the cell culture medium of HUVECs. However, inhibiting p-Akt Ser473 had no effect on eNOS phosphorylation at Ser1177. Next, we administered mice with inhibitors to downregulate p-Akt Ser473 or Thr308 activity. Along with the inhibition of p-Akt Thr308, vascular p-eNOS Ser1177 protein was simultaneously downregulated in parallel with a decrease in plasma NO concentration. Additionally, we cultured HUVECs at various temperature conditions (37, 22, and 4 °C). The results showed that p-Akt Ser473 was gradually decreased in line with the reduction in temperature, accompanied by increased levels of p-Akt Thr308 and p-eNOS Ser1177. Taken together, our study indicates that the phosphorylation of Akt at Thr308, but not at Ser473, plays a more significant role in regulating p-eNOS Ser1177 levels under physiological conditions.
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