钙调蛋白依赖性蛋白激酶 II 对肌浆网磷蛋白和 SR Ca2+负荷的调节作用。
CaMKII regulation of phospholamban and SR Ca2+ load.
机构信息
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, La Plata, Argentina.
出版信息
Heart Rhythm. 2011 May;8(5):784-7. doi: 10.1016/j.hrthm.2010.11.035. Epub 2010 Nov 23.
Abstract
Phospholamban (PLN) is a small phosphoprotein in the cardiac sarcoplasmic reticulum (SR). Dephosphorylated PLN tonically inhibits the SR Ca-ATPase (SERCA2a) and phosphorylation of PLN, at either Ser by PKA or Thr by Ca-calmodulin-dependent protein kinase (CaMKII), reverses this inhibition. Consequently, there are increases in SERCA2a activity, SR Ca uptake rate and SR Ca load. Through this mechanism, PLN is a major regulator of basal cardiac Ca cycling, contractility and relaxation and the main determinant of β-adrenergic mechanical responses in the heart. In this article, we briefly review the functional role of CaMKII-dependent PLN phosphorylation at Thr site and the new findings that link this phosphorylation to beneficial or detrimental effects in pathophysiological situations.
摘要
磷酸化调节蛋白（PLN）是心肌肌浆网（SR）中的一种小磷酸化蛋白。去磷酸化的 PLN 对 SR Ca-ATP 酶（SERCA2a）产生紧张性抑制，而 PLN 的磷酸化，不论是由蛋白激酶 A（PKA）在丝氨酸上磷酸化，还是由钙调蛋白依赖性蛋白激酶（CaMKII）在苏氨酸上磷酸化，均可逆转这种抑制。因此，SR Ca 摄取率和 SR Ca 负荷增加，SERCA2a 活性增加。通过这种机制，PLN 是心脏基础 Ca 循环、收缩和舒张的主要调节剂，也是心脏β肾上腺素能机械反应的主要决定因素。在本文中，我们简要回顾了 CaMKII 依赖性 PLN 在苏氨酸位点磷酸化的功能作用，以及将这种磷酸化与病理生理情况下有益或有害影响联系起来的新发现。
相似文献
1
CaMKII regulation of phospholamban and SR Ca2+ load.钙调蛋白依赖性蛋白激酶 II 对肌浆网磷蛋白和 SR Ca2+负荷的调节作用。
Heart Rhythm. 2011 May;8(5):784-7. doi: 10.1016/j.hrthm.2010.11.035. Epub 2010 Nov 23.
2
Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart. Role of Ca2+/calmodulin-dependent protein kinase II.细胞内钙离子（Ca2+）增加和肌浆网（SR）钙负荷增加促成大鼠心脏酸中毒后的心律失常。钙调蛋白依赖性蛋白激酶II的作用。
Am J Physiol Heart Circ Physiol. 2008 Oct;295(4):H1669-83. doi: 10.1152/ajpheart.00010.2008. Epub 2008 Aug 22.
3
Ablation of phospholamban rescues reperfusion arrhythmias but exacerbates myocardium infarction in hearts with Ca2+/calmodulin kinase II constitutive phosphorylation of ryanodine receptors.肌浆网钙转运蛋白磷蛋白（phospholamban）消融能挽救再灌注心律失常，但会加重心肌肌浆网钙释放通道（ryanodine receptor）钙/钙调蛋白激酶 II 组成性磷酸化所致的心肌梗死。
Cardiovasc Res. 2019 Mar 1;115(3):556-569. doi: 10.1093/cvr/cvy213.
4
A Single Protein Kinase A or Calmodulin Kinase II Site Does Not Control the Cardiac Pacemaker Ca2+ Clock.单一的蛋白激酶A或钙调蛋白激酶II位点并不控制心脏起搏器Ca2+时钟。
Circ Arrhythm Electrophysiol. 2016 Feb;9(2):e003180. doi: 10.1161/CIRCEP.115.003180.
5
Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure.钙/钙调蛋白依赖性蛋白激酶调节心力衰竭时心肌兰尼碱受体的磷酸化及肌浆网钙泄漏。
Circ Res. 2005 Dec 9;97(12):1314-22. doi: 10.1161/01.RES.0000194329.41863.89. Epub 2005 Nov 3.
6
Phospholamban phosphorylation by CaMKII under pathophysiological conditions.病理生理条件下钙调蛋白激酶II对受磷蛋白的磷酸化作用。
Front Biosci. 2008 May 1;13:5988-6005. doi: 10.2741/3131.
7
Calcium-calmodulin-dependent protein kinase mediates the intracellular signalling pathways of cardiac apoptosis in mice with impaired glucose tolerance.钙调蛋白依赖性蛋白激酶介导糖耐量受损小鼠心脏细胞凋亡的细胞内信号通路。
J Physiol. 2017 Jun 15;595(12):4089-4108. doi: 10.1113/JP273714. Epub 2017 Mar 2.
8
Phospholamban ablation rescues sarcoplasmic reticulum Ca(2+) handling but exacerbates cardiac dysfunction in CaMKIIdelta(C) transgenic mice.肌浆网钙转运蛋白磷酸酶抑制因子基因敲除可改善钙调蛋白依赖性激酶 IIdelta(C)转基因小鼠的心肌舒张功能障碍，但恶化心肌的钙离子处理能力。
Circ Res. 2010 Feb 5;106(2):354-62. doi: 10.1161/CIRCRESAHA.109.207423. Epub 2009 Dec 3.
9
CaMKII-dependent phosphorylation of cardiac ryanodine receptors regulates cell death in cardiac ischemia/reperfusion injury.钙调蛋白激酶II介导的心肌兰尼碱受体磷酸化调控心肌缺血/再灌注损伤中的细胞死亡。
J Mol Cell Cardiol. 2014 Sep;74:274-83. doi: 10.1016/j.yjmcc.2014.06.004. Epub 2014 Jun 17.
10
Calcium/calmodulin-dependent protein kinase II mediates cardioprotection of intermittent hypoxia against ischemic-reperfusion-induced cardiac dysfunction.钙/钙调蛋白依赖性蛋白激酶II介导间歇性低氧对缺血再灌注诱导的心脏功能障碍的心脏保护作用。
Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H735-42. doi: 10.1152/ajpheart.01164.2008. Epub 2009 Jun 12.
引用本文的文献
1
Structure-function relationships and modifications of cardiac sarcoplasmic reticulum Ca2+-transport.心脏肌浆网 Ca2+转运的结构-功能关系和修饰。
Physiol Res. 2021 Dec 30;70(Suppl4):S443-S470. doi: 10.33549/physiolres.934805.
2
Phosphoprotein Phosphatase 1 but Not 2A Activity Modulates Coupled-Clock Mechanisms to Impact on Intrinsic Automaticity of Sinoatrial Nodal Pacemaker Cells.磷酸蛋白磷酸酶 1 而非 2A 活性调节偶联时钟机制以影响窦房结起搏细胞的固有自发性。
Cells. 2021 Nov 10;10(11):3106. doi: 10.3390/cells10113106.
3
Altered Ca and Na Homeostasis in Human Hypertrophic Cardiomyopathy: Implications for Arrhythmogenesis.人类肥厚型心肌病中钙和钠稳态的改变：对心律失常发生机制的影响。
Front Physiol. 2018 Oct 16;9:1391. doi: 10.3389/fphys.2018.01391. eCollection 2018.
4
Two-pore Channels (TPC2s) and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) at Lysosomal-Sarcoplasmic Reticular Junctions Contribute to Acute and Chronic β-Adrenoceptor Signaling in the Heart.溶酶体-肌浆网连接处的双孔通道（TPC2s）和烟酰胺腺嘌呤二核苷酸磷酸（NAADP）对心脏急性和慢性β-肾上腺素能受体信号传导有贡献。
J Biol Chem. 2015 Dec 11;290(50):30087-98. doi: 10.1074/jbc.M115.684076. Epub 2015 Oct 5.
5
Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation.正常的心脏收缩和舒张需要组成型脑源性神经营养因子/酪氨酸激酶受体B（BDNF/TrkB）信号传导。
Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1880-5. doi: 10.1073/pnas.1417949112. Epub 2015 Jan 12.
6
Synthetic phosphopeptides enable quantitation of the content and function of the four phosphorylation states of phospholamban in cardiac muscle.合成磷酸肽可定量心肌中受磷蛋白四种磷酸化状态的含量和功能。
J Biol Chem. 2014 Oct 17;289(42):29397-405. doi: 10.1074/jbc.M114.556621. Epub 2014 Sep 4.
7
Inhibition of CaMKII does not attenuate cardiac hypertrophy in mice with dysfunctional ryanodine receptor.抑制钙调蛋白依赖性蛋白激酶II（CaMKII）并不能减轻患有功能失调的兰尼碱受体的小鼠的心脏肥大。
PLoS One. 2014 Aug 5;9(8):e104338. doi: 10.1371/journal.pone.0104338. eCollection 2014.
8
CaMKII-dependent responses to ischemia and reperfusion challenges in the heart.心脏中钙/钙调蛋白依赖性蛋白激酶II对缺血和再灌注应激的反应。
Front Pharmacol. 2014 May 6;5:96. doi: 10.3389/fphar.2014.00096. eCollection 2014.
9
The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias.钙调蛋白依赖性蛋白激酶 II 抑制在心脏病中的应用前景：预防心力衰竭和心律失常。
Expert Opin Ther Targets. 2013 Aug;17(8):889-903. doi: 10.1517/14728222.2013.809064. Epub 2013 Jun 24.
10
A Memory Molecule, Ca(2+)/Calmodulin-Dependent Protein Kinase II and Redox Stress; Key Factors for Arrhythmias in a Diseased Heart.一种记忆分子，钙离子/钙调蛋白依赖性蛋白激酶 II 和氧化应激；疾病心脏中心律失常的关键因素。
Korean Circ J. 2013 Mar;43(3):145-51. doi: 10.4070/kcj.2013.43.3.145.
本文引用的文献
1
The signalling pathway of CaMKII-mediated apoptosis and necrosis in the ischemia/reperfusion injury.钙调蛋白依赖性蛋白激酶 II 介导热缺血/再灌注损伤中细胞凋亡和坏死的信号通路。
J Mol Cell Cardiol. 2010 Jun;48(6):1298-306. doi: 10.1016/j.yjmcc.2009.12.015. Epub 2010 Jan 6.
2
Phospholamban ablation rescues sarcoplasmic reticulum Ca(2+) handling but exacerbates cardiac dysfunction in CaMKIIdelta(C) transgenic mice.肌浆网钙转运蛋白磷酸酶抑制因子基因敲除可改善钙调蛋白依赖性激酶 IIdelta(C)转基因小鼠的心肌舒张功能障碍，但恶化心肌的钙离子处理能力。
Circ Res. 2010 Feb 5;106(2):354-62. doi: 10.1161/CIRCRESAHA.109.207423. Epub 2009 Dec 3.
3
Calmodulin kinase II inhibition protects against structural heart disease.钙调蛋白激酶II抑制可预防结构性心脏病。
Nat Med. 2005 Apr;11(4):409-17. doi: 10.1038/nm1215. Epub 2005 Mar 27.
4
Immunodetection of phosphorylation sites gives new insights into the mechanisms underlying phospholamban phosphorylation in the intact heart.磷酸化位点的免疫检测为完整心脏中受磷蛋白磷酸化的潜在机制提供了新的见解。
J Biol Chem. 1996 Dec 27;271(52):33561-7. doi: 10.1074/jbc.271.52.33561.
5
Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation.受磷蛋白基因的靶向消融与心肌收缩力显著增强及β-激动剂刺激丧失有关。
Circ Res. 1994 Sep;75(3):401-9. doi: 10.1161/01.res.75.3.401.
Zotero 插件