Mitochondrial Dysfunction-Associated Arrhythmogenic Substrates in Diabetes Mellitus

Song, Jiajia; Yang, Ruilin; Yang, Jing; Zhou, Lufang

doi:10.3389/fphys.2018.01670

Cited by 14 publications

(10 citation statements)

References 136 publications

(166 reference statements)

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“…Clinical data have demonstrated that there is a bidirectional relationship between diabetes mellitus and cardiovascular diseases, as well as heart failure ( Song et al, 2018 ). Various factors associated with diabetes mellitus, such as impaired calcium homeostasis, altered free fatty acid metabolism, an unbalanced redox state, and increased advanced glycation end products, contribute to cardiovascular complications ( Riehle and Bauersachs, 2018 ; Zhang et al, 2018 ; Zheng et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, there is a great need to develop new anti-diabetic treatments and modify the existing therapeutic approaches (Sowton et al, 2019) in order to attenuate the complications of diabetes, especially microvascular complications (retinopathy, nephropathy, and neuropathy), macrovascular complications (ischemic heart disease, stroke, and peripheral vascular disease), and the diminished quality of life (Heusch, 2018;Karwi et al, 2018). Clinical data have demonstrated that there is a bidirectional relationship between diabetes mellitus and cardiovascular diseases, as well as heart failure (Song et al, 2018). Various factors associated with diabetes mellitus, such as impaired calcium homeostasis, altered free fatty acid metabolism, an unbalanced redox state, and increased advanced glycation end products, contribute to cardiovascular complications (Riehle and Bauersachs, 2018;Zhang et al, 2018;Zheng et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

et al. 2021

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Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

et al. 2021

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“…Mitochondria influence cellular physiology in a variety of ways (41), and are involved in many pathologies, including epilepsy (152,153), thyroid function (154), cancer (155)(156)(157)(158), diabetes (159,160), and BrS (41), among others. Mitochondria produce adenosine triphosphate (ATP), which is required for protein phosphorylation, a process that is required for normal protein function (161).…”

Section: Mitochondria and Brugada Syndromementioning

confidence: 99%

Brugada Syndrome: Warning of a Systemic Condition?

D'Imperio

Monasky

Micaglio

et al. 2021

Front. Cardiovasc. Med.

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Brugada syndrome (BrS) is a hereditary disorder, characterized by a specific electrocardiogram pattern and highly related to an increased risk of sudden cardiac death. BrS has been associated with other cardiac and non-cardiac pathologies, probably because of protein expression shared by the heart and other tissue types. In fact, the most commonly found mutated gene in BrS, SCN5A, is expressed throughout nearly the entire body. Consistent with this, large meals and alcohol consumption can trigger arrhythmic events in patients with BrS, suggesting a role for organs involved in the digestive and metabolic pathways. Ajmaline, a drug used to diagnose BrS, can have side effects on non-cardiac tissues, such as the liver, further supporting the idea of a role for organs involved in the digestive and metabolic pathways in BrS. The BrS electrocardiogram (ECG) sign has been associated with neural, digestive, and metabolic pathways, and potential biomarkers for BrS have been found in the serum or plasma. Here, we review the known associations between BrS and various organ systems, and demonstrate support for the hypothesis that BrS is not only a cardiac disorder, but rather a systemic one that affects virtually the whole body. Any time that the BrS ECG sign is found, it should be considered not a single disease, but rather the final step in any number of pathways that ultimately threaten the patient's life. A multi-omics approach would be appropriate to study this syndrome, including genetics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, and glycomics, resulting eventually in a biomarker for BrS and the ability to diagnose this syndrome using a minimally invasive blood test, avoiding the risk associated with ajmaline testing.

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“…In diabetes, mitochondria increase the production of reactive oxygen species (ROS), thus causing oxidative stress and tissue damage (21). Mitochondrial damage may even precede hyperglycemia in diabetes (28). These data suggest that mitochondrial dysfunction may be a common pathway of diabetes and I/R injury severity.…”

Section: Introductionmentioning

confidence: 99%

Diabetes aggravates renal ischemia-reperfusion injury by repressing mitochondrial function and PINK1/Parkin-mediated mitophagy

Yang

Gong

Zhang

et al. 2019

American Journal of Physiology-Renal Physiology

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Diabetes could aggravate ischemia-reperfusion (I/R) injury, but the underlying mechanism is unclear. In the present study, we aimed to investigate whether diabetes exacerbates renal I/R injury and its possible mechanism. In vitro, HK-2 cells under normal or high glucose conditions were subjected to hypoxia (12 h) followed by reoxygenation (3 h) (H/R). Cell viability, intracellular ATP content, mitochondrial membrane potential, reactive oxygen species production, and apoptosis were measured. In vivo, streptozotocin-induced diabetic and nondiabetic rats were subjected to I/R. Renal pathology, function, and apoptosis were evaluated by hematoxylin and eosin staining, transmission electron microscopy, and Western blot analysis. Compared with the normal glucose + H/R group, mitochondrial function (ATP, mitochondrial membrane potential, and reactive oxygen species) and mitophagy were reduced in the high glucose + H/R group, as was expression of phosphatase and tensin homolog-induced putative kinase 1 (PINK1) and Parkin. Also, cells in the high glucose + H/R group exhibited more apoptosis compared with the normal glucose + H/R group, as assessed by flow cytometry, TUNEL staining, and Western blot analysis. Compared with normal rats that underwent I/R, diabetic rats that underwent I/R exhibited more severe tubular damage and renal dysfunction as well as expression of the apoptotic protein caspase-3. Meanwhile, diabetes alleviated mitophagy-associated protein expression in rats subjected to I/R, including expression of PINK1 and Parkin. Transmission electron microscopy indicated that the mitophagosome could be hardly observed and that mitochondrial morphology and structure were obviously damaged in the diabetes + I/R group. In conclusion, our results, for the first time, indicate that diabetes could aggravate I/R injury by repressing mitochondrial function and PINK1/Parkin-mediated mitophagy in vivo and in vitro.

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Mitochondrial Dysfunction-Associated Arrhythmogenic Substrates in Diabetes Mellitus

Cited by 14 publications

References 136 publications

RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

Brugada Syndrome: Warning of a Systemic Condition?

Diabetes aggravates renal ischemia-reperfusion injury by repressing mitochondrial function and PINK1/Parkin-mediated mitophagy

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