Vangheluwe Peter, Schuermans Marleen, Zádor Ernö, Waelkens Etienne, Raeymaekers Luc, Wuytack Frank
Laboratory of Physiology, O/N Gasthuisberg, K.U. Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Biochem J. 2005 Jul 1;389(Pt 1):151-9. doi: 10.1042/BJ20050068.
The widely held view that SLN (sarcolipin) would be the natural inhibitor of SERCA1 (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase 1), and PLB (phospholamban) its counterpart for SERCA2 inhibition is oversimplified and partially wrong. The expression of SLN and PLB mRNA and protein relative to SERCA1 or SERCA2 was assessed in ventricle, atrium, soleus and EDL (extensor digitorum longus) of mouse, rat, rabbit and pig. SLN protein levels were quantified by means of Western blotting using what appears to be the first successfully generated antibody directed against SLN. Our data confirm the co-expression of PLB and SERCA2a in cardiac muscle and the very low levels (in pig and rabbit) or the absence (in rat and mouse) of PLB protein in the slow skeletal muscle. In larger animals, the SLN mRNA and protein expression in the soleus and EDL correlates with SERCA1a expression, but, in rodents, SLN mRNA and protein show the highest abundance in the atria, which are devoid of SERCA1. In the rodent atria, SLN could therefore potentially interact with PLB and SERCA2a. No SLN was found in the ventricles of the different species studied, and there was no compensatory SLN up-regulation for the loss of PLB in PLB(-/-) mouse. In addition, we found that SLN expression was down-regulated at the mRNA and protein level in the atria of hypertrophic hearts of SERCA2(b/b) mice. These data suggest that superinhibition of SERCA by PLB-SLN complexes could occur in the atria of the smaller rodents, but not in those of larger animals.
普遍认为肌浆球蛋白（SLN）是肌浆网/内质网Ca2 + -ATP酶1（SERCA1）的天然抑制剂，而受磷蛋白（PLB）是SERCA2的对应抑制剂，这种观点过于简单化且部分错误。在小鼠、大鼠、兔子和猪的心室、心房、比目鱼肌和趾长伸肌（EDL）中评估了SLN和PLB mRNA及蛋白相对于SERCA1或SERCA2的表达。通过蛋白质印迹法，使用似乎是首个成功制备的针对SLN的抗体对SLN蛋白水平进行了定量。我们的数据证实了PLB和SERCA2a在心肌中的共表达，以及慢肌中PLB蛋白水平极低（在猪和兔子中）或不存在（在大鼠和小鼠中）。在较大动物中，比目鱼肌和EDL中SLN mRNA和蛋白表达与SERCA1a表达相关，但在啮齿动物中，SLN mRNA和蛋白在不含SERCA1的心房中丰度最高。因此，在啮齿动物心房中，SLN可能与PLB和SERCA2a相互作用。在所研究的不同物种的心室中均未发现SLN，并且在PLB基因敲除（PLB(-/-)）小鼠中，未发现因PLB缺失而导致的SLN代偿性上调。此外，我们发现，在SERCA2(b/b)小鼠肥厚性心脏的心房中，SLN表达在mRNA和蛋白水平均下调。这些数据表明，PLB - SLN复合物对SERCA的超抑制可能发生在较小啮齿动物的心房中，但在较大动物的心房中则不会发生。
