Vittone Leticia, Mundina-Weilenmann Cecilia, Mattiazzi Alicia
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Medicas, Universidad Nacional de La Plata, 60 y 120, 1900 La Plata, Argentina.
Front Biosci. 2008 May 1;13:5988-6005. doi: 10.2741/3131.
Sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a) transports Ca2+ into the SR, decreasing the cytosolic Ca2+ during relaxation and increasing the SR Ca2+ available for contraction. SERCA2a activity is regulated by phosphorylation of another SR protein: Phospholamban (PLN). Dephosphorylated PLN inhibits SERCA2a. Phosphorylation of PLN by either cAMP or cGMP-dependent protein kinase at Ser16 or the Ca2+-calmodulin-dependent protein kinase (CaMKII), at Thr17, relieves this inhibition, increasing SR Ca2+ uptake and SR Ca2+ load. Thus, PLN is a major player in the regulation of myocardial relaxation and contractility. This review will examine the main aspects of the role of CaMKII and Thr17 site of PLN, on different pathophysiological conditions: acidosis, ischemia/reperfusion (I/R) and heart failure (HF). Whereas CaMKII-activation and PLN phosphorylation contribute to the functional recovery during acidosis and stunning, CaMKII results detrimental in the irreversible I/R injury, producing apoptosis and necrosis. Phosphorylation of Thr17 residue of PLN and CaMKII activity vary in the different models of HF. The possible role of these changes in the depressed cardiac function of HF will be discussed.
肌浆网（SR）Ca2+ATP酶（SERCA2a）将Ca2+转运至肌浆网，在舒张期降低胞浆Ca2+浓度，并增加可供收缩利用的肌浆网Ca2+含量。SERCA2a的活性受另一种肌浆网蛋白——受磷蛋白（PLN）磷酸化的调节。去磷酸化的PLN抑制SERCA2a。cAMP或cGMP依赖性蛋白激酶在丝氨酸16位点使PLN磷酸化，或Ca2+ - 钙调蛋白依赖性蛋白激酶（CaMKII）在苏氨酸17位点使PLN磷酸化，均可解除这种抑制作用，增加肌浆网Ca2+摄取和肌浆网Ca2+负荷。因此，PLN是心肌舒张和收缩性调节中的主要参与者。本综述将探讨CaMKII和PLN苏氨酸17位点在不同病理生理状态（酸中毒、缺血/再灌注（I/R）和心力衰竭（HF））中的作用的主要方面。虽然CaMKII激活和PLN磷酸化有助于酸中毒和心肌顿抑时的功能恢复，但CaMKII在不可逆的I/R损伤中是有害的，可导致细胞凋亡和坏死。在不同的HF模型中，PLN苏氨酸17残基的磷酸化和CaMKII活性各不相同。将讨论这些变化在HF心脏功能减退中的可能作用。
