APA
Click to copy
Collins, H. E., Pat, B. M., Zou, L., Litovsky, S., Wende, A., Young, M., & Chatham, J. (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
Click to copy
Collins, Helen E, Betty M Pat, Luyun Zou, S. Litovsky, A. Wende, M. Young, and J. 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
Click to copy
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, S. and Wende, A. and Young, M. and Chatham, J.}
}
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.
