PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 Receptors
Background/Aims: High-density lipoproteins (HDL) exert multiple cardioprotective functions on the arterial wall, including the promotion of endothelial cell survival and proliferation. Among mechanism contributing to endothelial protection, it has been reported that apolipoprotein A-I (apoA-I), the...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-06-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/477607 |
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| author | Audrey Castaing-Berthou Nicole Malet Claudia Radojkovic Cendrine Cabou Stéphanie Gayral Laurent Olivier Martinez Muriel Laffargue |
| author_facet | Audrey Castaing-Berthou Nicole Malet Claudia Radojkovic Cendrine Cabou Stéphanie Gayral Laurent Olivier Martinez Muriel Laffargue |
| author_sort | Audrey Castaing-Berthou |
| collection | DOAJ |
| description | Background/Aims: High-density lipoproteins (HDL) exert multiple cardioprotective functions on the arterial wall, including the promotion of endothelial cell survival and proliferation. Among mechanism contributing to endothelial protection, it has been reported that apolipoprotein A-I (apoA-I), the major protein in HDL, binds and activates the endothelial ecto-F1-ATPase receptor. This generates extracellular ADP, which in turn promotes endothelial cell survival. In this study we aimed to further investigate the signaling pathway involved downstream of apoA-I-induced ecto-F1-ATPase activation. Methods: In human umbilical vein endothelial cells (HUVECs), pharmacological and gene silencing approaches were used to study pathways involved downstream ecto-F1-ATPase activation by apoA-I. Results: ApoA-I and HDL both induced Akt phosphorylation. F1-ATPase inhibitors such as inhibitory factor 1 and oligomycin completely blocked apoA-I-induced Akt phosphorylaton and significantly blocked HDL-induced phosphorylation, indicating that this signaling pathway is dependent on ecto-F1-ATPase activation by apoA-I. Further, we were able to specify roles for the P2Y1-ADPreceptor and the PI3Kβ isoform in this pathway since pharmacological inhibition and silencing of these proteins dramatically inhibited apoA-I-induced Akt phosphorylation and cell proliferation. Conclusion: Altogether, these data highlight a key role of the P2Y1/PI3Kβ axis in endothelial cell proliferation downstream of ecto-F1-ATPase activation by apoA-I. Pharmacological targeting of this pathway could represent a promising approach to enhance vascular endothelial protection. |
| first_indexed | 2024-12-14T20:56:01Z |
| format | Article |
| id | doaj.art-2bbe027da883465bacb125d6bc1dd117 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-14T20:56:01Z |
| publishDate | 2017-06-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-2bbe027da883465bacb125d6bc1dd1172022-12-21T22:47:41ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-06-0142257959310.1159/000477607477607PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 ReceptorsAudrey Castaing-BerthouNicole MaletClaudia RadojkovicCendrine CabouStéphanie GayralLaurent Olivier MartinezMuriel LaffargueBackground/Aims: High-density lipoproteins (HDL) exert multiple cardioprotective functions on the arterial wall, including the promotion of endothelial cell survival and proliferation. Among mechanism contributing to endothelial protection, it has been reported that apolipoprotein A-I (apoA-I), the major protein in HDL, binds and activates the endothelial ecto-F1-ATPase receptor. This generates extracellular ADP, which in turn promotes endothelial cell survival. In this study we aimed to further investigate the signaling pathway involved downstream of apoA-I-induced ecto-F1-ATPase activation. Methods: In human umbilical vein endothelial cells (HUVECs), pharmacological and gene silencing approaches were used to study pathways involved downstream ecto-F1-ATPase activation by apoA-I. Results: ApoA-I and HDL both induced Akt phosphorylation. F1-ATPase inhibitors such as inhibitory factor 1 and oligomycin completely blocked apoA-I-induced Akt phosphorylaton and significantly blocked HDL-induced phosphorylation, indicating that this signaling pathway is dependent on ecto-F1-ATPase activation by apoA-I. Further, we were able to specify roles for the P2Y1-ADPreceptor and the PI3Kβ isoform in this pathway since pharmacological inhibition and silencing of these proteins dramatically inhibited apoA-I-induced Akt phosphorylation and cell proliferation. Conclusion: Altogether, these data highlight a key role of the P2Y1/PI3Kβ axis in endothelial cell proliferation downstream of ecto-F1-ATPase activation by apoA-I. Pharmacological targeting of this pathway could represent a promising approach to enhance vascular endothelial protection.http://www.karger.com/Article/FullText/477607ATP synthaseHDLApolipoprotein A-IPhosphoinositide 3-kinasePurinergic signalingEndothelial cell |
| spellingShingle | Audrey Castaing-Berthou Nicole Malet Claudia Radojkovic Cendrine Cabou Stéphanie Gayral Laurent Olivier Martinez Muriel Laffargue PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 Receptors Cellular Physiology and Biochemistry ATP synthase HDL Apolipoprotein A-I Phosphoinositide 3-kinase Purinergic signaling Endothelial cell |
| title | PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 Receptors |
| title_full | PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 Receptors |
| title_fullStr | PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 Receptors |
| title_full_unstemmed | PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 Receptors |
| title_short | PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 Receptors |
| title_sort | pi3kβ plays a key role in apolipoprotein a i induced endothelial cell proliferation through activation of the ecto f1 atpase p2y1 receptors |
| topic | ATP synthase HDL Apolipoprotein A-I Phosphoinositide 3-kinase Purinergic signaling Endothelial cell |
| url | http://www.karger.com/Article/FullText/477607 |
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