Interferon-γ and high glucose-induced opening of Cx43 hemichannels causes endothelial cell dysfunction and damage
| Autor: | Mauricio A. Retamal, Susana Contreras-Duarte, Juan C. Sáez, Juan A. Orellana, Cristian A. Santibañez, Victoria Velarde, Luis A. Mellado, Tanhia F. Alvear, Valeria C. Labra, Carla A. Inostroza |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Endothelium Connexin Inflammation Pharmacology Nitric Oxide Connexon Dinoprostone Nitric oxide Cell Line 03 medical and health sciences chemistry.chemical_compound Interferon-gamma 0302 clinical medicine Superoxides medicine Diabetes Mellitus Humans Insulin Molecular Biology Cell Death Superoxide Endothelial Cells Cell Biology Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Glucose chemistry Connexin 43 medicine.symptom 030217 neurology & neurosurgery Intracellular Signal Transduction |
| Zdroj: | Biochimica et biophysica acta. Molecular cell research. 1867(8) |
| ISSN: | 1879-2596 |
| Popis: | Both IFN-γ or high glucose have been linked to systemic inflammatory imbalance with serious repercussions not only for endothelial function but also for the formation of the atherosclerotic plaque. Although the uncontrolled opening of connexin hemichannels underpins the progression of various diseases, whether they are implicated in endothelial cell dysfunction and damage evoked by IFN-γ plus high glucose remains to be fully elucidated. In this study, by using live cell imaging and biochemical approaches, we demonstrate that IFN-γ plus high glucose augment endothelial connexin43 hemichannel activity, resulting in the increase of ATP release, ATP-mediated Ca2+ dynamics and production of nitric oxide and superoxide anion, as well as impaired insulin-mediated uptake and intercellular diffusion of glucose and cell survival. Based on our results, we propose that connexin 43 hemichannel inhibition could serve as a new approach for tackling the activation of detrimental signaling resulting in endothelial cell dysfunction and death caused by inflammatory mediators during atherosclerosis secondary to diabetes mellitus. |
| Databáze: | OpenAIRE |
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