Academic Journal
T-type Ca 2+ channels elicit pro-proliferative and anti-apoptotic responses through impaired PP2A/Akt1 signaling in PASMCs from patients with pulmonary arterial hypertension
| العنوان: | T-type Ca 2+ channels elicit pro-proliferative and anti-apoptotic responses through impaired PP2A/Akt1 signaling in PASMCs from patients with pulmonary arterial hypertension |
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| المؤلفون: | Sankhe, Safietou, Manousakidi, Sevasti, Antigny, Fabrice, Arthur Ataam, Jennifer, Bentebbal, Sana, Ruchon, Yann, Lecerf, Florence, Sabourin, Jessica, Price, Laura, Fadel, Elie, Dorfmüller, Peter, Eddahibi, Saadia, Humbert, Marc, Perros, Frédéric, Capuano, Véronique |
| المساهمون: | Centre Chirurgical Marie Lannelongue (CCML), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique (HPPIT), Université Paris-Sud - Paris 11 (UP11)-Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles U 1046 (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Pulmonary Hypertension Service, Royal Brompton Hospital, ANR-13-JSV1-0011,EMIR,Mécanismes épigénétiques dans l'inflammation et le remodelage vasculaire de l'hypertension pulmonaire(2013) |
| المصدر: | ISSN: 0167-4889 ; Biochimica et Biophysica Acta - Molecular Cell Research ; https://hal.umontpellier.fr/hal-01836102 ; Biochimica et Biophysica Acta - Molecular Cell Research, 2017, 1864 (10), pp.1631 - 1641. ⟨10.1016/j.bbamcr.2017.06.018⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | MAPkinase, Survivin, Lung, Caspase, Cell cycle, FoxO3A, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Idiopathic pulmonary arterial hypertension (iPAH) is characterized by obstructive hyperproliferation and apoptosis resistance of distal pulmonary artery smooth muscle cells (PASMCs). T-type Ca2+ channel blockers have been shown to reduce experimental pulmonary hypertension, although the impact of T-type channel inhibition remains unexplored in PASMCs from iPAH patients. Here we show that T-type channels Cav3.1 and Cav3.2 are present in the lung and PASMCs from iPAH patients and control subjects. The blockade of T-type channels by the specific blocker, TTA-A2, prevents cell cycle progression and PASMCs growth. In iPAH cells, T-type channel signaling fails to activate phosphatase PP2A, leading to an increase in ERK1/2, P38 activation. Moreover, T-type channel signaling is redirected towards the activation of the kinase Akt1, leading to increased expression of the anti-apoptotic protein survivin, and a decrease in the pro-apoptotic mediator FoxO3A. Finally, in iPAH cells, Akt1 is no longer able to regulate caspase 9 activation, whereas T-type channel overexpression reverses PP2A defect in iPAH cells but reinforces the deleterious effects of Akt1 activation. Altogether, these data highlight T-type channel signaling as a strong trigger of the pathological phenotype of PASMCs from iPAH patients (hyper-proliferation/cells survival and apoptosis resistance), suggesting that both T-type channels and PP2A may be promising therapeutic targets for pulmonary hypertension. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/28655554; PUBMED: 28655554 |
| DOI: | 10.1016/j.bbamcr.2017.06.018 |
| الاتاحة: | https://hal.umontpellier.fr/hal-01836102 https://hal.umontpellier.fr/hal-01836102v1/document https://hal.umontpellier.fr/hal-01836102v1/file/2017%20Sankhe%20et%20al.,%20T%20type%20of%20calcum%20channels.pdf https://doi.org/10.1016/j.bbamcr.2017.06.018 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.24117A4A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.bbamcr.2017.06.018 |
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