دورية أكاديمية
Receptor Interacting Protein 3 Suppresses Vascular Smooth Muscle Cell Growth by Inhibition of the Phosphoinositide 3-Kinase-Akt Axis
| العنوان: | Receptor Interacting Protein 3 Suppresses Vascular Smooth Muscle Cell Growth by Inhibition of the Phosphoinositide 3-Kinase-Akt Axis |
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| المؤلفون: | Li, Qian, Li, Geng, Lan, Xiaomei, Zheng, Ming, Chen, Kuang-Hueih, Cao, Chun-Mei, Xiao, Rui-Ping |
| المساهمون: | Cao, CM (reprint author), Peking Univ, Inst Mol Med, Beijing 100083, Peoples R China., Peking Univ, Inst Mol Med, Beijing 100083, Peoples R China., Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China., NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. |
| المصدر: | EI ; SCI ; PubMed |
| بيانات النشر: | journal of biological chemistry |
| سنة النشر: | 2010 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | NF-KAPPA-B, ANGIOTENSIN-CONVERTING ENZYME, RIP-LIKE KINASE, NEOINTIMAL HYPERPLASIA, BALLOON ANGIOPLASTY, DEATH DOMAIN, APOPTOSIS, AKT, PROLIFERATION, RESTENOSIS |
| الوصف: | Proliferation of vascular smooth muscle cells (VSMCs) is a primary mechanism underlying cardiovascular proliferative disorders. Phosphoinositide 3-kinase (PI3K)-Akt (or protein kinase B) axis has been assigned at the center of pathways that regulate cell proliferation. Here we demonstrate that enhanced PI3K-Akt signaling by mitogenic stimulation or arterial injury profoundly elevates expression of receptor interacting protein 3 (RIP3) in primary cultured rat VSMCs and in vivo and that the up-regulation of RIP3 leads toVSMCgrowth arrest and apoptosis via inhibiting the PI3K-Akt signaling pathway, thereby alleviating balloon injury-induced neointimal formation. Specifically, mitogenic stimulation with platelet-derived growth factor-BB or angiotensin II leads to a profound increase in RIP3 expression, which is abolished by inhibition of PI3K or Akt, and increased PI3K-Akt signaling by expression of a constitutively active PI3K mutant also elevates RIP3 expression. Importantly, adenoviral overexpression of RIP3 not only triggers apoptosis but also causes cell cycle arrest at G(1)/G(0) phases that is associated with suppressed Akt activation. In sharp contrast, RIP3 gene silencing enhances serum- and platelet-derived growth factor-induced cell proliferation and Akt activation. In vivo adenoviral gene delivery of rat RIP3 (rRIP3) increased apoptosis and reduced VSMC proliferation, thus, effectively alleviating balloon injury-induced neointimal formation. The growth-suppressive and pro-apoptotic effects are independent of rRIP3 Ser/Thr kinase activity, because overexpression of a kinase-in-active mutant of rRIP3, similar to its wild type, is sufficient to induce growth arrest and apoptosis. These findings reveal a novel growth-suppressive action of RIP3, marking RIP3 as an important factor to prevent excessive mitogenic stimulation- or injury-induced vascular smooth muscle cells hyperplasia. ; Biochemistry & Molecular Biology ; SCI(E) ; EI ; PubMed ; 8 ; ARTICLE ; 13 ; 9535-9544 ; 285 |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 0021-9258 |
| العلاقة: | JOURNAL OF BIOLOGICAL CHEMISTRY.2010,285,(13),9535-9544.; 671049; http://hdl.handle.net/20.500.11897/345055Test; WOS:000276165900027 |
| DOI: | 10.1074/jbc.M109.071332 |
| الإتاحة: | https://doi.org/20.500.11897/345055Test https://doi.org/10.1074/jbc.M109.071332Test https://hdl.handle.net/20.500.11897/345055Test |
| رقم الانضمام: | edsbas.3E37266B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00219258 |
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| DOI: | 10.1074/jbc.M109.071332 |