ArticleAmerican journal of physiology. Heart and circulatory physiology2008
Akt activates NOS3 and separately restores barrier integrity in H2O2-stressed human cardiac microvascular endothelium.
Article in American journal of physiology. Heart and circulatory physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
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- The association between dietary intakes of nitrate with nitrite from animal and plant food sources and the incidence of pre-diabetes and type 2 diabetes: a prospective study.Nutrition & metabolism · 2025Article
- CEACAM1 in vascular homeostasis and inflammation.European journal of clinical investigation · 2024Review
- Association of Urinary Nitrate With Diabetes Complication and Disease-Specific Mortality Among Adults With Hyperglycemia.The Journal of clinical endocrinology and metabolism · 2023Article
- Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3.Science translational medicine · 2021Article
- A Computational Exploration of the Molecular Network Associated to Neuroinflammation in Alzheimer's Disease.Frontiers in pharmacology · 2021Article
- Wall stretch and thromboxane A₂ activate NO synthase (eNOS) in pulmonary arterial smooth muscle cells via H₂O₂ and Akt-dependent phosphorylation.Pflugers Archiv : European journal of physiology · 2016Article
- Endothelial Barrier and Its Abnormalities in Cardiovascular Disease.Frontiers in physiology · 2015Review
- Role of c-Met/phosphatidylinositol 3-kinase (PI3k)/Akt signaling in hepatocyte growth factor (HGF)-mediated lamellipodia formation, reactive oxygen species (ROS) generation, and motility of lung endothelial cells.The Journal of biological chemistry · 2014Article
- Regulation of cardiac nitric oxide signaling by nuclear β-adrenergic and endothelin receptors.Journal of molecular and cellular cardiology · 2013Article
- Interplay between Hepatitis C Virus and Redox Cell Signaling.International journal of molecular sciences · 2013Article
- Phospholipase D signaling mediates reactive oxygen species-induced lung endothelial barrier dysfunction.Pulmonary circulation · 2013Article
- Role of reactive oxygen and nitrogen species in the vascular responses to inflammation.Free radical biology & medicine · 2012Review
- Article
- Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Annexin 2 regulates endothelial morphogenesis by controlling AKT activation and junctional integrity.The Journal of biological chemistry · 2010Article
- Akt1 genetic deficiency limits hypothermia cardioprotection following murine cardiac arrest.American journal of physiology. Heart and circulatory physiology · 2010Article
- Angiotensin II impairs endothelial function via tyrosine phosphorylation of the endothelial nitric oxide synthase.The Journal of experimental medicine · 2009Article
- Rapid aldosterone signaling and vascular reactivity: relax or don't do it.Journal of cardiovascular pharmacology · 2009Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The integrity of microvascular endothelium is an important regulator of myocardial contractility. Microvascular barrier integrity could be altered by increased reactive oxygen species (ROS) stress seen within minutes after cardiac arrest resuscitation. Akt and its downstream target nitric oxide (NO) synthase (NOS)3 can protect barrier integrity during ROS stress, but little work has studied these oxidant stress responses in human cardiac microvascular endothelial cells (HCMVEC). We, therefore, studied how ROS affects barrier function and NO generation via Akt and its downstream target NOS3 in HCMVEC. HCMVEC exposed to 500 microM H2O2 had increased Akt phosphorylation within 10 min at both Ser-473 and Thr-308 sites, an effect blocked by the phosphatidylinositol 3-kinase inhibitor LY-294002. H2O2 also induced NO generation that was associated with NOS3 Ser-1177 site phosphorylation and Thr-495 dephosphorylation, with Ser-1177 effects attenuated by LY-294002 and an Akt inhibitor, Akt/PKB signaling inhibitor-2 (API-2). H2O2 induced significant barrier disruption in HCMVEC within minutes, but recovery started within 30 min and normalized over hours. The NOS inhibitor Nomega-nitro-L-arginine methyl ester (200 microM) blocked NO generation but had no effect on H2O2-induced barrier permeability or the recovery of barrier integrity. By contrast, the Akt inhibitor API-2 abrogated HCMVEC barrier restoration. These results suggest that oxidant stress in HCMVEC activates NOS3 via Akt. NOS3/NO are not involved in the regulation of H2O2-affected barrier function in HCMVEC. Independent of NOS3 regulation, Akt proves to be critical for the restoration of barrier integrity in HCMVEC.
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