Methazolamide Attenuates the Development of Diabetic Cardiomyopathy by Promoting β-Catenin Degradation in Type 1 Diabetic Mice

Chen, Xiaoqing; Li, Yilang; Yuan, Wenchang; Li, Conglin; Zeng, Yue; Lian, Yuling; Qiu, Xiaoxia; Qin, Yuan; Zhang, Guiping; Liu, Xia-Wen; Luo, Cheng; Luo, Jia; Hou, Ning

doi:10.2337/db21-0506

Cited by 9 publications

(7 citation statements)

References 41 publications

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“…The activation of canonical WNT and simultaneous removal of intracellular contacts synergistically stimulate cardiomyocyte proliferation. 172 The reactivation of WNT/β-catenin signaling occurs under different pathological conditions, such as (i) hypertensive heart disease, 79,173,174 (ii) diabetic cardiomyopathy, [175][176][177][178] (iii) heart failure that is caused by ischemic disease and myocardial infarction, 179,180 and (iv) autoimmune myocarditis. 181 Acute reactivation of the βcatenin signaling pathway via the adenovirus-mediated overexpression of constitutively active βcatenin is cardioprotective after myocardial infarction, reducing scar size, decreasing apoptosis, and improving contractile properties.…”

Section: Canonical Wnt Pathway In Postnatal Heart Growth and Heart Re...mentioning

confidence: 99%

“…175,176 The inhibition of βcatenin ameliorates the severity of heart failure. 178 The former mechanism was determined in colorectal cancer. High glucose concentrations lead to an increase in the O-GlcNAcylation of βcatenin at different sites, and Thr41 is the most important site for protein stability and transcriptional activity because of competition with GSK3β for phosphorylation.…”

Section: Inter Con Nec Tions Between Wnt/β-catenin Pathway and Glucos...mentioning

confidence: 99%

“…The development of diabetic cardiomyopathy is accompanied by activation of the WNT/β‐catenin signaling pathway 175,176 . The inhibition of β‐catenin ameliorates the severity of heart failure 178 . The former mechanism was determined in colorectal cancer.…”

Section: Interconnections Between Wnt/β‐catenin Pathway and Glucose M...mentioning

confidence: 99%

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WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

et al. 2023

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The WNT/β‐catenin pathway is a master regulator of cardiac development and growth, and its activity is low in healthy adult hearts. However, even this low activity is essential for maintaining normal heart function. Acute activation of the WNT/β‐catenin signaling cascade is considered to be cardioprotective after infarction through the upregulation of prosurvival genes and reprogramming of metabolism. Chronically high WNT/β‐catenin pathway activity causes profibrotic and hypertrophic effects in the adult heart. New data suggest more complex functions of β‐catenin in metabolic maturation of the perinatal heart, establishing an adult pattern of glucose and fatty acid utilization. Additionally, low basal activity of the WNT/β‐catenin cascade maintains oxidative metabolism in the adult heart, and this pathway is reactivated by physiological or pathological stimuli to meet the higher energy needs of the heart. This review summarizes the current state of knowledge of the organization of canonical WNT signaling and its function in cardiogenesis, heart maturation, adult heart function, and remodeling. We also discuss the role of the WNT/β‐catenin pathway in cardiac glucose, lipid metabolism, and mitochondrial physiology.

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Section: Canonical Wnt Pathway In Postnatal Heart Growth and Heart Re...mentioning

confidence: 99%

Section: Inter Con Nec Tions Between Wnt/β-catenin Pathway and Glucos...mentioning

confidence: 99%

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WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

et al. 2023

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“…It is believed to be related to oxidative stress, inflammation, myocardial apoptosis, autophagy and mitochondrial damage (Avagimyan et al, 2022). Many researchers have confirmed that β-catenin is involved in the development of DCM (Xi et al, 2015;Liu et al, 2020;Chen et al, 2022). In the DCM model induced by streptozotocin (STZ), the protein and mRNA expression levels of Wnt2, β-catenin, and c-Myc were increased in a time-dependent manner, as well as the expression of p-GSK3β (Xi et al, 2015).…”

Section: β-Catenin and Diabetic Cardiomyopathiesmentioning

confidence: 99%

The role of β-catenin in cardiac diseases

Sun²,

Zhao³

et al. 2023

Front. Pharmacol.

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The Wnt/β-catenin signaling pathway is a classical Wnt pathway that regulates the stability and nuclear localization of β-catenin and plays an important role in adult heart development and cardiac tissue homeostasis. In recent years, an increasing number of researchers have implicated the dysregulation of this signaling pathway in a variety of cardiac diseases, such as myocardial infarction, arrhythmias, arrhythmogenic cardiomyopathy, diabetic cardiomyopathies, and myocardial hypertrophy. The morbidity and mortality of cardiac diseases are increasing, which brings great challenges to clinical treatment and seriously affects patient health. Thus, understanding the biological roles of the Wnt/β-catenin pathway in these diseases may be essential for cardiac disease treatment and diagnosis to improve patient quality of life. In this review, we summarize current research on the roles of β-catenin in human cardiac diseases and potential inhibitors of Wnt/β-catenin, which may provide new strategies for cardiac disease therapies.

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“…A previous study demonstrated that they were divided into six groups with or without luteolin (5, 10, and 20 µM) and HGI-induced (glucose at 25.5 mM and insulin at 0.1 µM) for 48 h. The Con group was treated with corresponding amount of mannitol. All cells were cultured at 37°C with 5% CO 2 [15,22,27,28].…”

Section: Primary Culture Of Nrcmsmentioning

confidence: 99%

Luteolin Attenuates Diabetic Myocardial Hypertrophy by Inhibiting Proteasome Activity

Li¹,

Rekep²,

Tian³

et al. 2022

Pharmacology

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Introduction: Luteolin is a flavonoid polyphenolic compound exerting broad pharmacological and medicinal properties. Diabetes-related obesity increases the total blood volume and cardiac output and may increase the myocardial hypertrophy progression. However, the mechanism of luteolin in diabetic myocardial hypertrophy remains uncertain. Therefore, this study aimed to evaluate whether luteolin improved diabetic cardiomyopathy (DCM) by inhibiting the proteasome activity. Methods: Cardiomyopathy was induced in streptozotocin-treated diabetes mellitus (DM) and db/db mice. Luteolin (20 mg kg−1·day−1) was administrated via gavage for 12 weeks. In vitro, high glucose and high insulin (HGI, glucose at 25.5 mM and insulin at 0.1 µM) inducing primary neonatal rat cardiomyocytes (NRCMs) were treated with or without luteolin for 48 h. Echocardiography, reverse transcription quantitative polymerase chain reaction, histology, immunofluorescence, and Western blotting were conducted. Proteasome activities were also detected using a fluorescent peptide substrate. Results: Luteolin administration significantly prevented the onset of cardiac hypertrophy, fibrosis, and dysfunction in type 1 DM (T1DM) and type 2 DM (T2DM). Compared with DCM mice, luteolin groups showed lower serum triglyceride and total cholesterol levels. Furthermore, luteolin attenuated HGI-induced myocardial hypertrophy and reduced atrial natriuretic factor mRNA level in NRCMs. Proteasome activities were inhibited by luteolin in vitro. Luteolin also reduces the proteasome subunit levels (PSMB) 1, PSMB2, and PSMB5 of the 20S proteasome, as well as proteasome-regulated particles (Rpt) 1 and Rpt4 levels of 19S proteasome. Furthermore, luteolin treatment increased protein kinase B (AKT) and GSK-3α/β (inactivation of GSK-3) phosphorylation. The phosphorylation level of AMPK activity was also reversed after the treatment with luteolin in comparison with the HGI-treated group. Conclusion: This study indicates that luteolin protected against DCM in mice, including T1DM and T2DM, by upregulating phosphorylated protein AMPK and AKT/GSK-3 pathways while decreasing the proteasome activity. These findings suggest that luteolin may be a potential therapeutic agent for DCM.

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Methazolamide Attenuates the Development of Diabetic Cardiomyopathy by Promoting β-Catenin Degradation in Type 1 Diabetic Mice

Cited by 9 publications

References 41 publications

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

The role of β-catenin in cardiac diseases

Luteolin Attenuates Diabetic Myocardial Hypertrophy by Inhibiting Proteasome Activity

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