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Target Concepts:
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Query: UNIPROT:P31749 (
AKT
)
22,954
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The endoplasmic reticulum/sarcoplasmic reticulum Ca
2+
sensor stromal interaction molecule 1 (STIM1), a key mediator of store-operated Ca
2+
entry, is expressed in cardiomyocytes and has been implicated in regulating multiple cardiac processes, including hypertrophic signaling. Interestingly, cardiomyocyte-restricted deletion of STIM1 (
cr
STIM1-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
cr
STIM1-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
cr
STIM1-KO hearts. Despite similar rates of fatty acid oxidation in control and
cr
STIM1-KO hearts ex vivo,
cr
STIM1-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
cr
STIM1-KO hearts, consistent with cardiac insulin resistance. Interestingly, we observed abnormal mitochondria and increased lipid accumulation in 12-wk
cr
STIM1-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.
...
PMID:Novel role of the ER/SR Ca
2+
sensor STIM1 in the regulation of cardiac metabolism. 3057 37
