APA
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Collins, H. E., Pat, B. M., Zou, L., Litovsky, S. H., Wende, A. R., Young, M. E., & Chatham, J. C. (2019). Novel role of the ER/SR Ca2+ sensor STIM1 in the regulation of cardiac metabolism. American Journal of Physiology-Heart and Circulatory Physiology.
Chicago/Turabian
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Collins, Helen E., Betty M. Pat, Luyun Zou, Silvio H. Litovsky, Adam R. Wende, Martin E. Young, and John C. Chatham. “Novel Role of the ER/SR Ca2+ Sensor STIM1 in the Regulation of Cardiac Metabolism.” American Journal of Physiology-Heart and Circulatory Physiology (2019).
MLA
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Collins, Helen E., et al. “Novel Role of the ER/SR Ca2+ Sensor STIM1 in the Regulation of Cardiac Metabolism.” American Journal of Physiology-Heart and Circulatory Physiology, 2019.
BibTeX Click to copy
@article{helen2019a,
title = {Novel role of the ER/SR Ca2+ sensor STIM1 in the regulation of cardiac metabolism.},
year = {2019},
journal = {American Journal of Physiology-Heart and Circulatory Physiology},
author = {Collins, Helen E. and Pat, Betty M. and Zou, Luyun and Litovsky, Silvio H. and Wende, Adam R. and Young, Martin E. and Chatham, John C.}
}
The endoplasmic reticulum/sarcoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1), a key mediator of store-operated Ca2+ entry, is expressed in cardiomyocytes and has been implicated in regulating multiple cardiac processes, including hypertrophic signaling. Interestingly, cardiomyocyte-restricted deletion of STIM1 (crSTIM1-KO) results in age-dependent endoplasmic reticulum stress, altered mitochondrial morphology, and dilated cardiomyopathy in mice. Here, we tested the hypothesis that STIM1 deficiency may also impact cardiac metabolism. Hearts isolated from 20-wk-old crSTIM1-KO mice exhibited a significant reduction in both oxidative and nonoxidative glucose utilization. Consistent with the reduction in glucose utilization, expression of glucose transporter 4 and AMP-activated protein kinase phosphorylation were all reduced, whereas pyruvate dehydrogenase kinase 4 and pyruvate dehydrogenase phosphorylation were increased, in crSTIM1-KO hearts. Despite similar rates of fatty acid oxidation in control and crSTIM1-KO hearts ex vivo, crSTIM1-KO hearts contained increased lipid/triglyceride content as well as increased fatty acid-binding protein 4, fatty acid synthase, acyl-CoA thioesterase 1, hormone-sensitive lipase, and adipose triglyceride lipase expression compared with control hearts, suggestive of a possible imbalance between fatty acid uptake and oxidation. Insulin-mediated alterations in AKT phosphorylation were observed in crSTIM1-KO hearts, consistent with cardiac insulin resistance. Interestingly, we observed abnormal mitochondria and increased lipid accumulation in 12-wk crSTIM1-KO hearts, suggesting that these changes may initiate the subsequent metabolic dysfunction. These results demonstrate, for the first time, that cardiomyocyte STIM1 may play a key role in regulating cardiac metabolism. NEW & NOTEWORTHY Little is known of the physiological role of stromal interaction molecule 1 (STIM1) in the heart. Here, we demonstrate, for the first time, that hearts lacking cardiomyocyte STIM1 exhibit dysregulation of both cardiac glucose and lipid metabolism. Consequently, these results suggest a potentially novel role for STIM1 in regulating cardiac metabolism.