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This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: 297/2/H576    most recent 00946.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Jiao, Q. Articles by Minamisawa, S. PubMed PubMed Citation Articles by Jiao, Q. Articles by Minamisawa, S.

Sarcalumenin is essential for maintaining cardiac function during endurance exercise training

¹Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan; ²Department of Medical Chemistry, Kyoto University Graduate School of Pharmaceutical Science, Kyoto, Japan; ³Cardiovascular Research Institute, Departments of Cell Biology and Molecular Medicine and Medicine (Cardiology), New Jersey Medical School, Newark, New Jersey; ⁴Department of Life Science and Medical Bioscience, and ⁵Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan

Submitted 22 August 2008 ; accepted in final form 2 June 2009

Sarcalumenin (SAR), a Ca²⁺-binding protein located in the longitudinal sarcoplasmic reticulum (SR), regulates Ca²⁺ reuptake into the SR by interacting with cardiac sarco(endo)plasmic reticulum Ca²⁺-ATPase 2a (SERCA2a). We have previously demonstrated that SAR deficiency induced progressive heart failure in response to pressure overload, despite mild cardiac dysfunction in sham-operated SAR knockout (SARKO) mice (26). Since responses to physiological stresses often differ from those to pathological stresses, we examined the effects of endurance exercise on cardiac function in SARKO mice. Wild-type (WT) and SARKO mice were subjected to endurance treadmill exercise training (65% of maximal exercise ability for 60 min/day) for 12 wk. After exercise training, maximal exercise ability was significantly increased by 5% in WT mice (n = 6), whereas it was significantly decreased by 37% in SARKO mice (n = 5). Cardiac function assessed by echocardiographic examination was significantly decreased in accordance with upregulation of biomarkers of cardiac stress in SARKO mice after training. After training, expression levels of SERCA2a protein were significantly downregulated by 30% in SARKO hearts, whereas they were significantly upregulated by 59% in WT hearts. Consequently, SERCA2 activity was significantly decreased in SARKO hearts after training. Furthermore, the expression levels of other Ca²⁺-handling proteins, including phospholamban, ryanodine receptor 2, calsequestrin 2, and sodium/calcium exchanger 1, were significantly decreased in SARKO hearts after training. These results indicate that SAR plays a critical role in maintaining cardiac function under physiological stresses, such as endurance exercise, by regulating Ca²⁺ transport activity into the SR. SAR may be a primary target for exercise-related adaptation of the Ca²⁺ storage system in the SR to preserve cardiac function.

treadmill; calcium uptake; heart failure; excitation-contraction coupling