Elabela may regulate SIRT3‐mediated inhibition of oxidative stress through Foxo3a deacetylation preventing diabetic‐induced myocardial injury

Li, Cheng; Miao, Xiao; Wang, Shudong; Liu, Yucheng; Sun, Jian; Liu, Quan; Cai, Lu; Wang, Yonggang

doi:10.1111/jcmm.16052

Cited by 31 publications

(14 citation statements)

References 36 publications

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“…Diabetes mellitus, a metabolic disease characterized by chronic hyperglycemia resulting from insulin deficiency, is currently one of the most prevalent chronic medical conditions. Diabetes mellitus has been recognized as a major cardiovascular risk factor as it increases both cardiovascular morbidity and mortality ( Dia et al, 2020 ; Li et al, 2021 ). According to the American Diabetes Association, chronic hyperglycemia can cause long-term damage, dysfunction, and failure in various organs, including the eyes, kidneys, nerves, heart, and blood vessels.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Mitofusin-2 Enhances Mitochondrial Contact With the Endoplasmic Reticulum and Promotes Diabetic Cardiomyopathy

Zhang

Wang

2021

Front. Physiol.

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Diabetic cardiomyopathy has been associated with mitochondrial damage. Mitochondria–endoplasmic reticulum (ER) contact is an important determinant of mitochondrial function and ER homeostasis. We therefore investigated whether hyperglycemia can damage the mitochondria by increasing their contact with the ER in cardiomyocytes. We found that hyperglycemia induced mitochondria–ER contact in cardiomyocytes, as evidenced by the increased MMM1, MDM34, and BAP31 expressions. Interestingly, the silencing of Mfn2 reduced the cooperation between the mitochondria and the ER in cardiomyocytes. Mfn2 silencing improved cardiomyocyte viability and function under hyperglycemic conditions. Additionally, the silencing of Mfn2 markedly attenuated the release of calcium from the ER to the mitochondria, thereby preserving mitochondrial metabolism in cardiomyocytes under hyperglycemic conditions. Mfn2 silencing reduced mitochondrial reactive oxygen species production, which reduced mitochondria-dependent apoptosis in hyperglycemia-treated cardiomyocytes. Finally, Mfn2 silencing attenuated ER stress in cardiomyocytes subjected to high-glucose stress. These results demonstrate that Mfn2 promotes mitochondria–ER contact in hyperglycemia-treated cardiomyocytes. The silencing of Mfn2 sustained mitochondrial function, suppressed mitochondrial calcium overload, prevented mitochondrial apoptosis, and reduced ER stress, thereby enhancing cardiomyocyte survival under hyperglycemic conditions.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Mitofusin-2 Enhances Mitochondrial Contact With the Endoplasmic Reticulum and Promotes Diabetic Cardiomyopathy

Zhang

Wang

2021

Front. Physiol.

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“…A previous study showed that concentrations of 4-hydroxynonenal and malondialdehyde are high in the hearts of 8-week-old SIRT3 −/− mice, and that 4 weeks of antioxidant treatment normalizes the 4-hydroxynonenal concentration ( 81 ). In another study, the expression of MnSOD and catalase were found to be high in the hearts of SIRT3 overexpressing mice ( 84 ), while a third study showed that elabela (a novel peptide that has effects via the apelin receptor) may induce the inhibition of OS by SIRT3 through the deacetylation of FOXO3a, thereby preventing myocardial injury in diabetes ( 85 ). Taken together, these findings imply that SIRT3 inhibits OS in DCM.…”

Section: Oxidative Stress- Related Pathwaysmentioning

confidence: 99%

Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

Peng

et al. 2022

Front. Endocrinol.

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Diabetes is a chronic metabolic disease that is increasing in prevalence and causes many complications. Diabetic cardiomyopathy (DCM) is a complication of diabetes that is associated with high mortality, but it is not well defined. Nevertheless, it is generally accepted that DCM refers to a clinical disease that occurs in patients with diabetes and involves ventricular dysfunction, in the absence of other cardiovascular diseases, such as coronary atherosclerotic heart disease, hypertension, or valvular heart disease. However, it is currently uncertain whether the pathogenesis of DCM is directly attributable to metabolic dysfunction or secondary to diabetic microangiopathy. Oxidative stress (OS) is considered to be a key component of its pathogenesis. The production of reactive oxygen species (ROS) in cardiomyocytes is a vicious circle, resulting in further production of ROS, mitochondrial DNA damage, lipid peroxidation, and the post-translational modification of proteins, as well as inflammation, cardiac hypertrophy and fibrosis, ultimately leading to cell death and cardiac dysfunction. ROS have been shown to affect various signaling pathways involved in the development of DCM. For instance, OS causes metabolic disorders by affecting the regulation of PPARα, AMPK/mTOR, and SIRT3/FOXO3a. Furthermore, OS participates in inflammation mediated by the NF-κB pathway, NLRP3 inflammasome, and the TLR4 pathway. OS also promotes TGF-β-, Rho-ROCK-, and Notch-mediated cardiac remodeling, and is involved in the regulation of calcium homeostasis, which impairs ATP production and causes ROS overproduction. In this review, we summarize the signaling pathways that link OS to DCM, with the intention of identifying appropriate targets and new antioxidant therapies for DCM.

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“…Icariin has a cardioprotective effect in high-glucose-treated cardiomyocytes via upregulating apelin and SIRT3 expression, which can reverse diabetes-induced mitochondrial dysfunction; however, it did not affect the activity of SIRT3 in apelin silence samples ( 54 ). In addition, our previous research showed that Elabela can regulate the SIRT3-mediated inhibition of oxidative stress through Foxo3a deacetylation and prevent diabetic-induced myocardial injury ( 55 ). These results suggest that the apelin/SIRT3 signal pathway may be used as a novel therapeutic strategy for diabetes-related cardiovascular diseases.…”

Section: Effect Of Apelin–apj System On Diabetesmentioning

confidence: 99%

The Role of Apelin–APJ System in Diabetes and Obesity

Cheng

Adhikari³

et al. 2022

Front. Endocrinol.

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Nowadays, diabetes and obesity are two main health-threatening metabolic disorders in the world, which increase the risk for many chronic diseases. Apelin, a peptide hormone, exerts its effect by binding with angiotensin II protein J receptor (APJ) and is considered to be linked with diabetes and obesity. Apelin and its receptor are widely present in the body and are involved in many physiological processes, such as glucose and lipid metabolism, homeostasis, endocrine response to stress, and angiogenesis. In this review, we summarize the literatures on the role of the Apelin–APJ system in diabetes and obesity for a better understanding of the mechanism and function of apelin and its receptor in the pathophysiology of diseases that may contribute to the development of new therapies.

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Elabela may regulate SIRT3‐mediated inhibition of oxidative stress through Foxo3a deacetylation preventing diabetic‐induced myocardial injury

Cited by 31 publications

References 36 publications

RETRACTED: Mitofusin-2 Enhances Mitochondrial Contact With the Endoplasmic Reticulum and Promotes Diabetic Cardiomyopathy

RETRACTED: Mitofusin-2 Enhances Mitochondrial Contact With the Endoplasmic Reticulum and Promotes Diabetic Cardiomyopathy

Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

The Role of Apelin–APJ System in Diabetes and Obesity

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