Apoptosis of cardiomyocytes in diabetic cardiomyopathy involves overexpression of glycogen synthase kinase-3β

Wu, Wei; Liu, Xingxing; Han, Lei

doi:10.1042/bsr20171307

Cited by 21 publications

(14 citation statements)

References 31 publications

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“…It was suggested that suppressing expression of the lncRNA NKILA may inhibit the development of DC. 27 The apoptosis of cardiomyocytes under high-glucose conditions contributes to the pathogenesis of DC, 28 overexpression, as well as knockdown of the lncRNA NKILA accelerated and inhibited apoptotic cell death, respectively. 27 Compared with healthy subjects, patients with T2DM showed a more than fivefold increase in expression of the lncRNA NEAT1.…”

Section: Discussionmentioning

confidence: 99%

Circulating long non-coding RNAs NKILA, NEAT1, MALAT1, and MIAT expression and their association in type 2 diabetes mellitus

Alfaifi

Alshahrani

Ahmad

et al. 2021

BMJ Open Diab Res Care

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BackgroundType 2 diabetes mellitus (T2DM) is a multifactorial disorder that leads to alterations in gene regulation. Long non-coding RNAs (lncRNAs) have become a major research topic as they are involved in metabolic disorders.MethodsThis study included a total of 400 study subjects; 200 were subjects with T2DM and 200 were healthy subjects. Extracted RNA was used to synthesize cDNA by quantitative real time. Serum analysis was carried out to determine differences in biochemical parameters. Recorded data were used to evaluate associations with expression of lncRNAs NF-kappaB interacting lncRNA (NKILA), nuclear enriched abundant transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and myocardial infarction-associated transcript (MIAT) in T2DM cases.ResultsCompared with healthy controls, patients with T2DM showed an overall increase in expression of lncRNAs NKILA, NEAT, MALAT1, and MIAT by 3.94-fold, 5.28-fold, 4.46-fold, and 6.35-fold, respectively. Among patients with T2DM, higher expression of lncRNA NKILA was associated with hypertension (p=0.001), smoking (p<0.0001), and alcoholism (p<0.0001). Altered NEAT1 expression was significantly associated with weight loss (p=0.04), fatigue (p=0.01), slow wound healing (p=0.002), blurred vision (p=0.008), loss of appetite (p=0.007), smoking (p<0.0001), and alcoholism (p<0.0001). Higher expression of lncRNA MALAT1 was significantly linked with weight loss (p=0.003), blurred vision (p=0.01), smoking (p<0.0001), and alcoholism (p<0.0001). Expression of lncRNA MIAT was associated with only blurred vision (p<0.0001), smoking (p<0.0001), and alcoholism (p<0.0001). Positive correlations of lncRNA NKILA with lncRNAs NEAT1 (r=0.42, p<0.0001), MALAT (r=0.36, p<0.0001) and MIAT (r=0.42, p<0.0001) were observed among patients with T2DM. Significant positive correlations of lncRNA NEAT with lncRNAs MALAT and MIAT were observed among patients with T2DM. A positive correlation between lncRNAs MALAT and MIAT was also observed among patients with T2DM.ConclusionIncreased circulating NKILA, NEAT1, MALAT, and MIAT expression in patients with T2DM, which is linked with poor patient outcomes and significantly linked with alcoholism and smoking, may influence the degree and severity of disease among patients with T2DM. These lncRNAs may contribute to the progression of T2DM disease or other related diabetes-related complications.

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Section: Discussionmentioning

confidence: 99%

Circulating long non-coding RNAs NKILA, NEAT1, MALAT1, and MIAT expression and their association in type 2 diabetes mellitus

Alfaifi

Alshahrani

Ahmad

et al. 2021

BMJ Open Diab Res Care

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show abstract

“…Apoptosis of cardiomyocytes under a high-glucose environment contributes to the pathogenesis of DC (19), and inhibition of this pathophysiological process is considered to be a promising therapeutic target for DC (20). In the present study, it was illustrated that lncRNA NKILA overexpression and lncRNA NKILA knockdown accelerated and inhibited apoptotic cell death in cardiomyocytes under high-glucose treatment, respectively.…”

Section: Discussionmentioning

confidence: 99%

LncRNA NKILA was upregulated in diabetic cardiomyopathy with early prediction values

et al. 2019

Exp Ther Med

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Nuclear factor-κB interacting long non-coding RNA (LncRNA NKILA) is a well-studied tumor suppressor lncRNA in several types of malignancies. The present study reports the involvement of this lncRNA in diabetic cardiomyopathy (DC). A 8-year-follow-up study on 312 diabetic patients without exhibiting obvious complications demonstrated that plasma lncRNA NKILA levels were upregulated specifically in diabetic patients who developed DC but not in patients with other complications. Plasma levels of lncRNA NKILA at 6 months prior to diagnosis is sufficient to distinguish patients with DC from other diabetic patients without significant complications. Although in vitro experiments demonstrated that lncRNA NKILA expression in cardiomyocyte cells was not affected by high-glucose treatment, ectopic lncRNA NKILA expression and lncRNA NKILA knockdown potentiated, and inhibited cardiomyocyte apoptosis, respectively. Therefore, the data from the present study suggests that overexpression of lncRNA NKILA is involved in DC, and overexpression of lncRNA NKILA may serve as a therapeutic target for treating DC.

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“…Mechanisms responsible for the increased rates of apoptosis include increased production of ROS, endoplasmic reticulum stress, increased activation of the TGF-β1 signaling pathway, increased circulating inflammatory cytokines and chemokines, increased RAAS local activation, increased caspase activation, resistance to IGF-1 and altered expression of pro- and anti-apoptotic molecules [ 101 , 102 , 103 , 104 , 105 , 106 , 107 ]. Mitochondrial oxidative stress was found to be alleviated by metallothionein treatment in streptozotocin-treated mice, attenuating cell death [ 106 ]. Increased expression of glucose-regulated protein 78 (Grp78) and caspase12 in diabetic heart indicates the activation of endoplasmic reticulum-stress response that leads to cell death via apoptosis.…”

Section: Involvement Of Mitochondria Dysfunction In Diabetic Cardimentioning

confidence: 99%

“…Glycogen synthase kinase-3 β (GSK-3 β) induces apoptosis via activation of the apoptosis-related protease-caspase family and B-cell lymphoma 2 associated x-protein (BAX) genes [ 106 ]. Xu et al [ 107 ] reported that metformin was able to restore autophagic activity and inhibit cardiomyocyte apoptosis via disruption of B-cell lymphoma 2 (Bcl-2) and Beclin-1 complex in diabetic heart tissue.…”

Section: Involvement Of Mitochondria Dysfunction In Diabetic Cardimentioning

confidence: 99%

Mitochondrial Dysfunction in Diabetic Cardiomyopathy: The Possible Therapeutic Roles of Phenolic Acids

Jubaidi

Zainalabidin

Mariappan

et al. 2020

IJMS

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As the powerhouse of the cells, mitochondria play a very important role in ensuring that cells continue to function. Mitochondrial dysfunction is one of the main factors contributing to the development of cardiomyopathy in diabetes mellitus. In early development of diabetic cardiomyopathy (DCM), patients present with myocardial fibrosis, dysfunctional remodeling and diastolic dysfunction, which later develop into systolic dysfunction and eventually heart failure. Cardiac mitochondrial dysfunction has been implicated in the development and progression of DCM. Thus, it is important to develop novel therapeutics in order to prevent the progression of DCM, especially by targeting mitochondrial dysfunction. To date, a number of studies have reported the potential of phenolic acids in exerting the cardioprotective effect by combating mitochondrial dysfunction, implicating its potential to be adopted in DCM therapies. Therefore, the aim of this review is to provide a concise overview of mitochondrial dysfunction in the development of DCM and the potential role of phenolic acids in combating cardiac mitochondrial dysfunction. Such information can be used for future development of phenolic acids as means of treating DCM by alleviating the cardiac mitochondrial dysfunction.

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Apoptosis of cardiomyocytes in diabetic cardiomyopathy involves overexpression of glycogen synthase kinase-3β

Cited by 21 publications

References 31 publications

Circulating long non-coding RNAs NKILA, NEAT1, MALAT1, and MIAT expression and their association in type 2 diabetes mellitus

Circulating long non-coding RNAs NKILA, NEAT1, MALAT1, and MIAT expression and their association in type 2 diabetes mellitus

LncRNA NKILA was upregulated in diabetic cardiomyopathy with early prediction values

Mitochondrial Dysfunction in Diabetic Cardiomyopathy: The Possible Therapeutic Roles of Phenolic Acids

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