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中华妇幼临床医学杂志(电子版) ›› 2017, Vol. 13 ›› Issue (05) : 606 -610. doi: 10.3877/cma.j.issn.1673-5250.2017.05.019

所属专题: 文献

综述

PI3K-Akt3信号通路在心脏发育中的作用
陈焘1, 顾海涛1,()   
  1. 1. 210029 南京医科大学第一附属医院小儿心脏外科
  • 收稿日期:2017-05-07 修回日期:2017-08-21 出版日期:2017-10-01
  • 通信作者: 顾海涛

Roles of PI3K-Akt3 signaling pathway during cardiac development

Tao Chen1, Haitao Gu1,()   

  1. 1. Department of Pediatric Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
  • Received:2017-05-07 Revised:2017-08-21 Published:2017-10-01
  • Corresponding author: Haitao Gu
  • About author:
    Corresponding author: Gu Haitao, Email:
引用本文:

陈焘, 顾海涛. PI3K-Akt3信号通路在心脏发育中的作用[J]. 中华妇幼临床医学杂志(电子版), 2017, 13(05): 606-610.

Tao Chen, Haitao Gu. Roles of PI3K-Akt3 signaling pathway during cardiac development[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2017, 13(05): 606-610.

PI3K-Akt3信号通路是广泛存在于真核生物中高度保守的信号通路.PI3K-Akt3信号通路通过促进心肌细胞的生长和存活、促进冠脉血管新生、维持心脏收缩功能、调节信号转导和诱导细胞自噬等途径,在心脏发育中发挥重要作用。笔者拟就PI3K-Akt3信号通路对心脏发育影响的最新进展进行综述。

PI3K-Akt3 is a highly conservative signaling pathway, which exists widely in eukaryotes. PI3K-Akt3 signaling pathway plays an important role during cardiac development through the following ways: promoting cardiomyocyte growth and survival, promoting coronary angiogenesis, enhancing cardiac contractility, regulating signal transduction, inducing autophagy. In this review, we focus on the recent research progress about the roles of PI3K-Akt3 signaling pathway during cardiac development.

[1]
Liu J, Huang W, Ren C, et al. Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-κB and PI3K/Akt3 signaling pathways [J]. Sci Rep, 2015, 5: 11614.
[2]
Xue M, Ji X, Xue C, et al. Caspase-dependent and caspase-independent induction of apoptosis in breast cancer by fucoidan via the PI3K/AKT/GSK3β pathway in vivo and in vitro[J]. Biomed Pharmacother, 2017, 94: 898-908.
[3]
Balar AV, Iyer G, Al-Ahmadie H, et al. Alterations in the PI3K/Akt signaling pathway and association with outcome in invasive high-grade urothelial cancer (UC) [J]. J Clin Oncol, 2012, 30(5): 1255-1256.
[4]
Castillo SD, Vanhaesebroeck B, Sebire NJ. Phosphoinositide 3-kinase: a new kid on the block in vascular anomalies [J]. J Pathol, 2016, 240(4): 387-396.
[5]
Falasca M, Maffucci T. Regulation and cellular functions of class Ⅱ phosphoinositide 3-kinases [J]. Biochem J, 2012, 443(3): 587-601.
[6]
Schoijet AC, Sternlieb T, Alonso GD. The phosphatidylinositol 3-kinase class Ⅲ complex containing TcVps15 and TcVps34 participates in autophagy in trypanosoma cruzi [J]. J Eukaryot Microbiol, 2017, 64(3): 308-321.
[7]
Gonzalez E, McGraw TE. Insulin-modulated Akt subcellular localization determines Akt isoform-specific signaling [J]. Proc Natl Acad Sci USA, 2009, 106(17): 7004-7009.
[8]
Santi SA, Lee H. The Akt isoforms are present at distinct subcellular locations [J]. Am J Physiol Cell Physiol, 2010, 298(3): C580-C591.
[9]
Ding L, Biswas S, Morton RE, et al. Akt3 deficiency in macrophages promotes foam cell formation and atherosclerosis in mice [J]. Cell Metab, 2012, 15(6): 861-872.
[10]
Shioi T, Kang PM, Douglas PS, et al. The conserved phosphoinositide 3-kinase pathway determines heart size in mice [J]. EMBO J, 2000, 19(11): 2537-2548.
[11]
Bei Y, Zhou Q, Sun Q, et al. Exercise as a platform for pharmacotherapy development in cardiac diseases [J]. Curr Pharm Des, 2015, 21(30): 4409-4416.
[12]
Wu J, Li D, Du L, et al. Ouabain prevents pathological cardiac hypertrophy and heart failure through activation of phosphoinositide 3-kinase α in mouse [J]. Cell Biosci, 2015, 5: 64.
[13]
McMullen JR, Shioi T, Huang WY, et al. The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase (p110alpha) pathway [J]. J Biol Chem, 2004, 279(6): 4782-4793.
[14]
Crackower MA, Oudit GY, Kozieradzki I, et al. Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways [J]. Cell, 2002, 110(6): 737-749.
[15]
McMullen JR, Amirahmadi F, Woodcock EA, et al. Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy [J]. Proc Natl Acad Sci USA, 2007, 104(2): 612-617.
[16]
Lin RC, Weeks KL, Gao XM, et al. PI3K(p110 alpha) protects against myocardial infarction-induced heart failure: identification of PI3K-regulated miRNA and mRNA [J]. Arterioscler Thromb Vasc Biol, 2010, 30(4): 724-732.
[17]
Mohan ML, Jha BK, Gupta MK, et al. Phosphoinositide 3-kinase γ inhibits cardiac GSK-3 independently of Akt [J]. Sci Signal, 2013, 6(259): ra4.
[18]
Zhabyeyev P, McLean B, Patel VB, et al. Dual loss of PI3Kα and PI3Kγ signaling leads to an age-dependent cardiomyopathy [J]. J Mol Cell Cardiol, 2014, 77: 155-159.
[19]
Matsui T, Li L, Wu JC, et al. Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart [J]. J Biol Chem, 2002, 277(25): 22896-22901.
[20]
Shioi T, McMullen JR, Kang PM, et al. Akt/protein kinase B promotes organ growth in transgenic mice [J]. Mol Cell Biol, 2002, 22(8): 2799-2809.
[21]
Condorelli G, Drusco A, Stassi G, et al. Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice [J]. Proc Natl Acad Sci USA, 2002, 99(19): 12333-12338.
[22]
Taniyama Y, Ito M, Sato K, et al. Akt3 overexpression in the heart results in progression from adaptive to maladaptive hypertrophy [J]. J Mol Cell Cardiol, 2005, 38(2): 375-385.
[23]
Bekhite MM, Finkensieper A, Binas S, et al. VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells [J]. J Cell Sci, 2011, 124(Pt 11): 1819-1830.
[24]
Lelievre E, Bourbon PM, Duan LJ, et al. Deficiency in the p110alpha subunit of PI3K results in diminished Tie2 expression and Tie2(-/-)-like vascular defects in mice [J]. Blood, 2005,105(10): 3935-3938.
[25]
Shiojima I, Sato K, Izumiya Y, et al. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure [J]. J Clin Invest, 2005, 115(8): 2108-2118.
[26]
Liang W, Oudit GY, Patel MM, et al. Role of phosphoinositide 3-kinase (alpha), protein kinase C, and L-type Ca2+ channels in mediating the complex actions of angiotensin Ⅱ on mouse cardiac contractility [J]. Hypertension, 2010, 56(3): 422-429.
[27]
Lee TM, Lin SZ, Chang NC. Effect of lithium on ventricular remodelling in infarcted rats via the Akt/mTOR signalling pathways [J]. Biosci Rep, 2017, 37(2), pii: BSR20160257.
[28]
Sun H, Kerfant BG, Zhao D, et al. Insulin-like growth factor-1 and PTEN deletion enhance cardiac L-type Ca2+ currents via increased PI3Kalpha/PKB signaling [J]. Circ Res, 2006, 98(11): 1390-1397.
[29]
Yano N, Tseng A, Zhao TC, et al. Temporally controlled overexpression of cardiac-specific PI3Kalpha induces enhanced myocardial contractility--a new transgenic model [J]. Am J Physiol Heart Circ Physiol, 2008, 295(4): H1690-H1694.
[30]
Lu Z, Jiang YP, Wang W, et al. Loss of cardiac phosphoinositide 3-kinase p110α results in contractile dysfunction [J]. Circulation, 2009, 120(4): 318-325.
[31]
Wu CY, Jia Z, Wang W, et al. PI3Ks maintain the structural integrity of T-tubules in cardiac myocytes [J]. PLoS One, 2011, 6(9): e24404.
[32]
Pretorius L, Du XJ, Woodcock EA, et al. Reduced phosphoinositide 3-kinase (p110alpha) activation increases the susceptibility to atrial fibrillation [J]. Am J Pathol, 2009, 175(3): 998-1009.
[33]
Vasudevan NT, Mohan ML, Gupta MK, et al. Inhibition of protein phosphatase 2A activity by PI3Kγ regulates β-adrenergic receptor function [J]. Mol Cell, 2011, 41(6): 636-648.
[34]
Perino A, Ghigo A, Ferrero E, et al. Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110γ [J]. Mol Cell, 2011, 42(1): 84-95.
[35]
Su D, Zhou Y, Hu S, et al. Role of GAB1/PI3K/AKT signaling high glucose-induced cardiomyocyte apoptosis [J]. Biomed Pharmacother, 2017, 93: 1197-1204.
[36]
Ghigo A, Laffargue M, Li M. PI3K and calcium signaling in cardiovascular disease[J]. Circ Res2017, 121: 282-292.
[37]
Hirsch E, Braccini L, Ciraolo E, et al. Twice upon a time: PI3K′s secret double life exposed [J]. Trends Biochem Sci, 2009, 34(5): 244-248.
[38]
Mohan ML, Naga Prasad SV. Scaffolding function of PI3Kgamma emerges from enzyme's shadow [J]. J Mol Biol, 2017, 429(6): 763-772.
[39]
Madeddu P, Kraenkel N, Barcelos LS, et al. Phosphoinositide 3-kinase gamma gene knockout impairs postischemic neovascularization and endothelial progenitor cell functions [J]. Arterioscler Thromb Vasc Biol, 2008, 28(1): 68-76.
[40]
D'Andrea I, Fardella V, Fardella S, et al. Lack of kinase-independent activity of PI3Kγ in locus coeruleus induces ADHD symptoms through increased CREB signaling [J]. EMBO Mol Med, 2015, 7(7): 904-917.
[41]
Ghigo A, Perino A, Mehel H, et al. Phosphoinositide 3-kinase γ protects against catecholamine-induced ventricular arrhythmia through protein kinase A-mediated regulation of distinct phosphodiesterases [J]. Circulation, 2012, 126(17): 2073-2783.
[42]
Santulli G, Marks AR. Essential roles of intracellular calcium release channels in muscle, brain, metabolism, and aging [J]. Curr Mol Pharmacol, 2015, 8(2): 206-222.
[43]
Ciraolo E, Iezzi M, Marone R, et al. Phosphoinositide 3-kinase p110beta activity: key role in metabolism and mammary gland cancer but not development [J]. Sci Signal, 2008, 1(36): ra3.
[44]
Jia S, Liu Z, Zhang S, et al. Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis [J]. Nature, 2008, 454(7205): 776-779.
[45]
Dou Z, Chattopadhyay M, Pan JA, et al. The class ⅠA phosphatidylinositol 3-kinase p110-beta subunit is a positive regulator of autophagy [J]. J Cell Biol, 2010, 191(4): 827-843.
[46]
Dou Z, Pan JA, Dbouk HA, et al. Class ⅠA PI3K p110β subunit promotes autophagy through Rab5 small GTPase in response to growth factor limitation[J]. Molecular Cell, 2013, 50(1):29.
[47]
Jaber N, Dou Z, Chen JS, et al. Class Ⅲ PI3K Vps34 plays an essential role in autophagy and in heart and liver function [J]. Proc Natl Acad Sci USA, 2012, 109(6): 2003-2008.
[48]
Ghigo A, Franco I, Morello F, et al. Myocyte signalling in leucocyte recruitment to the heart [J]. Cardiovasc Res, 2014, 102(2): 270-280.
[49]
Fougerat A, Gayral S, Gourdy P, et al. Genetic and pharmacological targeting of phosphoinositide 3-kinase-gamma reduces atherosclerosis and favors plaque stability by modulating inflammatory processes [J]. Circulation, 2008, 117(10): 1310-1317.
[50]
Damilano F, Franco I, Perrino C, et al. Distinct effects of leukocyte and cardiac phosphoinositide 3-kinase γ activity in pressure overload-induced cardiac failure [J]. Circulation, 2011, 123(4): 391-399.
[51]
Yoshioka K, Yoshida K, Cui H, et al. Endothelial PI3K-C2α,a class Ⅱ PI3K, has an essential role in angiogenesis and vascular barrier function [J]. Nat Med, 2012, 18(10): 1560-1569.
[52]
Franco I, Gulluni F, Campa CC, et al. PI3K class Ⅱ α controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function [J]. Dev Cell, 2014, 28(6): 647-658.
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