ArticlePloS one2008
ATP release from vascular endothelia occurs across Cx43 hemichannels and is attenuated during hypoxia.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 133 citations in OpenAlex.
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Cx43 hemichannel-mediated paracrine involves in the promotion of MSCs on skin wound healing.Stem cell research & therapy · 2025Article
- Regulation of the Angiogenic Potential of Endothelial Cells In Vitro under Conditions of Acute Hypoxic Stress: The Role of Homotypic Communication via Gap Junctions.Bulletin of experimental biology and medicine · 2025Article
- Progressive Deactivation of Hydroxylases Controls Hypoxia-Inducible Factor-1α-Coordinated Cellular Adaptation to Graded Hypoxia.Research (Washington, D.C.) · 2025Article
- Potential of Adora2b as an immunotherapeutic target for gastric cancer.Frontiers in immunology · 2025Review
- Connexin 43 across the Vasculature: Gap Junctions and Beyond.Journal of vascular research · 2023Review
- The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.Biomedicines · 2022Review
- The mechanisms through which auricular vagus nerve stimulation protects against cerebral ischemia/reperfusion injury.Neural regeneration research · 2022Article
- Review
- Alternative adenosine Receptor activation: The netrin-Adora2b link.Frontiers in pharmacology · 2022Review
- The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells.Frontiers in immunology · 2022Review
- PANX1 is a potential prognostic biomarker associated with immune infiltration in pancreatic adenocarcinoma: A pan-cancer analysis.Channels (Austin, Tex.) · 2021Article
- Purinergic signaling in the modulation of redox biology.Redox biology · 2021Review
- Purinergic signaling in diabetes and metabolism.Biochemical pharmacology · 2021Review
- Purinergic Signaling in Liver Pathophysiology.Frontiers in endocrinology · 2021Review
- Polarized Proteins in Endothelium and Their Contribution to Function.Journal of vascular research · 2021Review
- Review
- TRPC Channels in Cardiac Plasticity.Cells · 2020Review
- Eosinophils and Purinergic Signaling in Health and Disease.Frontiers in immunology · 2020Review
- TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy.Scientific reports · 2019Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExtracellular ATP is an important signaling molecule for vascular adaptation to limited oxygen availability (hypoxia). Here, we pursued the contribution of vascular endothelia to extracellular ATP release under hypoxic conditions. METHODOLOGY, PRINCIPAL
findingsWe gained first insight from studying ATP release from endothelia (HMEC-1) pre-exposed to hypoxia. Surprisingly, we found that ATP release was significantly attenuated following hypoxia exposure (2% oxygen, 22+/-3% after 48 h). In contrast, intracellular ATP was unchanged. Similarly, lactate-dehydrogenase release into the supernatants was similar between normoxic or hypoxic endothelia, suggesting that differences in lytic ATP release between normoxia or hypoxia are minimal. Next, we used pharmacological strategies to study potential mechanisms for endothelial-dependent ATP release (eg, verapamil, dipyridamole, 18-alpha-glycyrrhetinic acid, anandamide, connexin-mimetic peptides). These studies revealed that endothelial ATP release occurs--at least in part--through connexin 43 (Cx43) hemichannels. A real-time RT-PCR screen of endothelial connexin expression showed selective repression of Cx43 transcript and additional studies confirmed time-dependent Cx43 mRNA, total and surface protein repression during hypoxia. In addition, hypoxia resulted in Cx43-serine368 phosphorylation, which is known to switch Cx43 hemi-channels from an open to a closed state. CONCLUSIONS/SIGNIFICANCE: Taken together, these studies implicate endothelial Cx43 in hypoxia-associated repression of endothelial ATP release.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.