Ca2+/calmodulin-dependent protein kinase II inhibition reduces myocardial fatty acid uptake and oxidation after myocardial infarction

Meng, Yidi; Ding, Peiwu; Wang, Hongfei; Yang, Xueke; Wang, Zhiyu; Nie, Daan; Liu, Jie; Huang, Yuhang; Su, Guanhua; Hu, Jun; Su, Yanwen; Du, Xiaoxiao; Dong, Nianguo; Jia, Haibo; Zhang, Hongbing; Zhang, Jiaming; Li, Jingdong

doi:10.1016/j.bbalip.2022.159120

Cited by 3 publications

(5 citation statements)

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“…Additionally, the reduced 13 C enrichment from [U-13 C]glucose metabolism was least pronounced in citrate (−12.8%) and glutamine (−12.9%), which are markers of astrocyte metabolism in slices (McNair et al, 2017). Given that synaptic plasticity and memory formation are highly energy requiring processes (Karbowski, 2019;Plaçais et al, 2017), the observed reduced oxi- reported to regulate the activity of AMP-activated protein kinase (AMPK) (Raney & Turcotte, 2008), whereas CaMKII was suggested to regulate AMPK activity in the heart (Meng et al, 2022). In both instances, activation of the CaMKII-AMPK pathway was shown to regulate fatty acid metabolism (Meng et al, 2022;Raney & Turcotte, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Given that synaptic plasticity and memory formation are highly energy requiring processes (Karbowski, 2019;Plaçais et al, 2017), the observed reduced oxi- reported to regulate the activity of AMP-activated protein kinase (AMPK) (Raney & Turcotte, 2008), whereas CaMKII was suggested to regulate AMPK activity in the heart (Meng et al, 2022). In both instances, activation of the CaMKII-AMPK pathway was shown to regulate fatty acid metabolism (Meng et al, 2022;Raney & Turcotte, 2008). Indeed, AMPK serves as a master metabolic switch, which upon activation promotes catabolic pathways and ATP generation (Ronnett et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Deletion of CaMKIIα may mediate acute effects by altered protein phosphorylation, but changes in transcriptional activity and post‐natal neurodevelopmental effects may also contribute. In skeletal muscle, CaMKII signaling has been reported to regulate the activity of AMP‐activated protein kinase (AMPK) (Raney & Turcotte, 2008), whereas CaMKII was suggested to regulate AMPK activity in the heart (Meng et al, 2022). In both instances, activation of the CaMKII‐AMPK pathway was shown to regulate fatty acid metabolism (Meng et al, 2022; Raney & Turcotte, 2008).…”

Section: Discussionmentioning

confidence: 99%

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Deletion of CaMKIIα disrupts glucose metabolism, glutamate uptake, and synaptic energetics in the cerebral cortex

Andersen

Westi

Griem-Krey

et al. 2023

Journal of Neurochemistry

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Ca2+/calmodulin‐dependent protein kinase II alpha (CaMKIIα) is a key regulator of neuronal signaling and synaptic plasticity. Synaptic activity and neurotransmitter homeostasis are closely coupled to the energy metabolism of both neurons and astrocytes. However, whether CaMKIIα function is implicated in brain energy and neurotransmitter metabolism remains unclear. Here, we explored the metabolic consequences of CaMKIIα deletion in the cerebral cortex using a genetic CaMKIIα knockout (KO) mouse. Energy and neurotransmitter metabolism was functionally investigated in acutely isolated cerebral cortical slices using stable 13C isotope tracing, whereas the metabolic function of synaptosomes was assessed by the rates of glycolytic activity and mitochondrial respiration. The oxidative metabolism of [U‐13C]glucose was extensively reduced in cerebral cortical slices of the CaMKIIα KO mice. In contrast, metabolism of [1,2‐13C]acetate, primarily reflecting astrocyte metabolism, was unaffected. Cellular uptake, and subsequent metabolism, of [U‐13C]glutamate was decreased in cerebral cortical slices of CaMKIIα KO mice, whereas uptake and metabolism of [U‐13C]GABA were unaffected, suggesting selective metabolic impairments of the excitatory system. Synaptic metabolic function was maintained during resting conditions in isolated synaptosomes from CaMKIIα KO mice, but both the glycolytic and mitochondrial capacities became insufficient when the synaptosomes were metabolically challenged. Collectively, this study shows that global deletion of CaMKIIα significantly impairs cellular energy and neurotransmitter metabolism, particularly of neurons, suggesting a metabolic role of CaMKIIα signaling in the brain.image

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Deletion of CaMKIIα disrupts glucose metabolism, glutamate uptake, and synaptic energetics in the cerebral cortex

Andersen

Westi

Griem-Krey

et al. 2023

Journal of Neurochemistry

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“…The cAMP [36] and cGMP-PKG [37] signaling pathways have been implicated in the pathophysiology of coronary atherosclerosis. In the cardiovascular system, an activated AMPK signaling pathway had a protective effect [38]. The pathological process of atherosclerosis includes lipid buildup, endothelial cell failure, inflammatory responses, monocyte recruitment, and aggregation, when monocytes become tissue-resident macrophages and foam cells when they adhere to modified low-density lipoprotein.…”

Section: Discussionmentioning

confidence: 99%

Identification of an Epigenetic Signature for Coronary Heart Disease in Postmenopausal Women’s PBMC DNA

Zhong

Song

Gao

et al. 2022

Mediators of Inflammation

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Menopause is accompanied with an increased risk of cardiovascular disease. DNA methylation may have a significant impact on postmenopausal women’s development of coronary heart disease. DNA methylation alterations in peripheral blood mononuclear cells (PBMCs) from women with coronary heart disease and healthy controls were detected using the Illumina Infinium MethylationEPIC BeadChip platform in this work. We employed Sangerbox technology and the GO and KEGG databases to further study the pathogenesis of coronary heart disease in postmenopausal women. After that, we used functional epigenetic module analysis and Cytoscape to remove the hub genes from the protein–protein interaction networks. Five genes (FOXA2, PTRD, CREB1, CTNAP2, and FBN2) were the hub genes. Lipid accumulation, endothelial cell failure, inflammatory responses, monocyte recruitment and aggregation, and other critical biological processes were all influenced by these genes. Finally, we employed methylation-specific PCR to demonstrate that FOXA2 was methylated at a high level in postmenopausal women with coronary heart disease. To better understand coronary heart disease in postmenopausal women’s molecular mechanisms, our study examine the major factors contributing to the state of DNA methylation modification, which will help discover novel diagnostic tools and treatment options.

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“…Malonyl CoA is an inhibitor of CPT‐1, the increase in ACC activity could promote the production of malonyl CoA, thereby suppressing cardiac fatty acid oxidation. In contrast to ACC, MCD converts malonyl CoA back to acetyl CoA, which could accelerate the rate of fatty acid oxidation and increase the generation of ATP in heart (Figure 1) (Meng et al, 2022; Ni et al, 2019). Of course, fatty acid oxidation mainly occurs in mitochondria, hence, the function of mitochondria is also the key factor to determine the levels of fatty acid oxidation.…”

Section: Overview Of Fatty Acid Metabolism In Heartmentioning

confidence: 99%

Fatty acid metabolism disorders and potential therapeutic traditional Chinese medicines in cardiovascular diseases

Liu

Zhang

et al. 2023

Phytotherapy Research

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Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid metabolism are crucial contributors in the development of cardiovascular diseases. The abnormal cardiac fatty acid metabolism usually leads to energy deficit, oxidative stress, excessive apoptosis, and inflammation. Targeting fatty acid metabolism has been regarded as a novel approach to the treatment of cardiovascular diseases. However, there are currently no specific drugs that regulate fatty acid metabolism to treat cardiovascular diseases. Many traditional Chinese medicines have been widely used to treat cardiovascular diseases in clinics. And modern studies have shown that they exert a cardioprotective effect by regulating the expression of key proteins involved in fatty acid metabolism, such as peroxisome proliferator‐activated receptor α and carnitine palmitoyl transferase 1. Hence, we systematically reviewed the relationship between fatty acid metabolism disorders and four types of cardiovascular diseases including heart failure, coronary artery disease, cardiac hypertrophy, and diabetic cardiomyopathy. In addition, 18 extracts and eight monomer components from traditional Chinese medicines showed cardioprotective effects by restoring cardiac fatty acid metabolism. This work aims to provide a reference for the finding of novel cardioprotective agents targeting fatty acid metabolism.

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Ca2+/calmodulin-dependent protein kinase II inhibition reduces myocardial fatty acid uptake and oxidation after myocardial infarction

Cited by 3 publications

References 45 publications

Deletion of CaMKIIα disrupts glucose metabolism, glutamate uptake, and synaptic energetics in the cerebral cortex

Deletion of CaMKIIα disrupts glucose metabolism, glutamate uptake, and synaptic energetics in the cerebral cortex

Identification of an Epigenetic Signature for Coronary Heart Disease in Postmenopausal Women’s PBMC DNA

Fatty acid metabolism disorders and potential therapeutic traditional Chinese medicines in cardiovascular diseases

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