부산대학교 도서관

The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is responsible for transporting calcium ([Ca.sup.2+]) from the cytosol into the lumen of the sarcoplasmic reticulum (SR) following muscular contraction. The [Ca.sup.2+] sequestering activity of SERCA facilitates muscular relaxation in both cardiac and skeletal muscle. There are more than 10 distinct isoforms of SERCA expressed in different tissues. SERCA2a is the primary isoform expressed in cardiac tissue, whereas SERCA1a is the predominant isoform expressed in fast-twitch skeletal muscle. The [Ca.sup.2+] sequestering activity of SERCA is regulated at the level of protein content and is further modified by the endogenous proteins phospholamban (PLN) and sarcolipin (SLN). Additionally, several novel mechanisms, including post-translational modifications and microRNAs (miRNAs) are emerging as integral regulators of [Ca.sup.2+] transport activity. These regulatory mechanisms are clinically relevant, as dysregulated SERCA function has been implicated in the pathology of several disease states, including heart failure. Currently, several clinical trials are underway that utilize novel therapeutic approaches to restore SERCA2a activity in humans. The purpose of this review is to examine the regulatory mechanisms of the SERCA pump, with a particular emphasis on the influence of exercise in preventing the pathological conditions associated with impaired SERCA function. Key words: calcium ([Ca.sup.2+]), cardiac muscle, skeletal muscle, phospholamban (PLN), sarcolipin (SLN), exercise, post-translational modifications, heart failure. L'ATPase SERCA (<>) est responsable du transport du calcium ([Ca.sup.2+]) du cytosol a la lumiere du reticulum sarcoplasmique (RS) a la suite de la contraction musculaire. L'activite de sequestration de [Ca.sup.2+] de SERCA facilite la relaxation musculaire tant dans le muscle cardiaque que dans le muscle squelettique. Il existe plus de 10 formes distinctes de SERCA exprimees dans differents tissus. SERCA2a est la principale isoforme exprimee dans le tissu cardiaque alors que SERCAla est l'isoforme predominante du muscle squelettique a contraction rapide. L'activite de sequestration de [Ca.sup.2+] de SERCA est regulee au niveau du contenu en proteine, et elle est modifiee en plus par deux proteines endogenes, le phospholamban (PLN) et la sarcolipine (SLN). En outre, plusieurs mecanismes nouveaux, dont les modifications posttraductionnelles et les microARN (miARN) emergent maintenant en tant que regulateurs integraux de l'activite de transport du [Ca.sup.2+]. Ces mecanismes regulateurs sont pertinents sur le plan clinique, car la deregulation de la fonction de SERCA a ete impliquee dans plusieurs pathologies incluant l'insuffisance cardiaque. Actuellement, plusieurs essais cliniques en cours utilisent de nouvelles approches therapeutiques afin de retablir l'activite de SERCA2a chez l'humain. Le but de cet article de revue est d'examiner les mecanismes regulateurs de la pompe SERCA, en mettant l'emphase sur l'influence de l'exercice dans la prevention des conditions pathologiques associees a une deficience de la fonction de SERCA. [Traduit par la Redaction] Mots-cles: calcium ([Ca.sup.2+]), muscle cardiaque, muscle squelettique, phospholamban (PLN), sarcolipine (SLN), exercice, modifications post-traductionnelles, insuffisance cardiaque.
Introduction The role of calcium in regulating muscular contraction Calcium ([Ca.sup.2+]) plays an integral role in regulating the process of excitation-contraction coupling (ECC) in both cardiac and skeletal muscle tissues. [...]