Metformin ameliorates ferroptosis in cardiac ischemia and reperfusion by reducing NOX4 expression via promoting AMPKα

Wu, Zhenhua; Bai, Yunpeng; Qi, Yujuan; Chang, Chia Chih; Jiao, Yan; Bai, Yaobang; Guo, Zhigang

doi:10.1080/13880209.2023.2212700

Cited by 11 publications

(3 citation statements)

References 27 publications

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“…Excessive oxidative stress including lipid peroxidation is the primary cause of ferroptosis [16]. In a rat model of myocardial IR, ferroptosis occurred, leading to worse heart function [17]. Tre inhibited ferroptosis via the NRF2/HO-1 pathway in a mouse model of spinal cord injury with reduced lipid peroxide production [18].…”

Section: Discussionmentioning

confidence: 99%

Effects of Trehalose Preconditioning on H9C2 Cell Viability and Autophagy Activation in a Model of Donation after Circulatory Death for Heart Transplantation

Gao,

Shingu,

Wakasa

2024

CIMB

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Donation after circulatory death (DCD) is a promising strategy for alleviating donor shortage in heart transplantation. Trehalose, an autophagy inducer, has been shown to be cardioprotective in an ischemia-reperfusion (IR) model; however, its role in IR injury in DCD remains unknown. In the present study, we evaluated the effects of trehalose on cardiomyocyte viability and autophagy activation in a DCD model. In the DCD model, cardiomyocytes (H9C2) were exposed to 1 h warm ischemia, 1 h cold ischemia, and 1 h reperfusion. Trehalose was administered before cold ischemia (preconditioning), during cold ischemia, or during reperfusion. Cell viability was measured using the Cell Counting Kit-8 after treatment with trehalose. Autophagy activation was evaluated by measuring autophagy flux using an autophagy inhibitor, chloroquine, and microtubule-associated protein 1A/1B light chain 3 B (LC3)-II by western blotting. Trehalose administered before the ischemic period (trehalose preconditioning) increased cell viability. The protective effects of trehalose preconditioning on cell viability were negated by chloroquine treatment. Furthermore, trehalose preconditioning increased autophagy flux. Trehalose preconditioning increased cardiomyocyte viability through the activation of autophagy in a DCD model, which could be a promising strategy for the prevention of cardiomyocyte damage in DCD transplantation.

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Section: Discussionmentioning

confidence: 99%

Effects of Trehalose Preconditioning on H9C2 Cell Viability and Autophagy Activation in a Model of Donation after Circulatory Death for Heart Transplantation

Gao,

Shingu,

Wakasa

2024

CIMB

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“…The underlying mechanisms involve the activation of AMPK and Nrf2 pathways (Ma et al, 2021;Yan J. et al, 2022;Sun Y. et al, 2023;Sun SP. et al, 2023;Liao et al, 2023;Peng et al, 2023;Wu et al, 2023). Vildagliptin has demonstrated the ability to upregulate the expression of GPX4 and improve ferroptosis in neurons (Zhang Y. et al, 2022), suggesting its possible inhibitory impact on DPP4 similar to p53 (87).…”

Section: Nutraceutical Approachesmentioning

confidence: 99%

Metabolic dysfunction-associated steatotic liver disease: ferroptosis related mechanisms and potential drugs

Zhu,

Wei,

Zhang

et al. 2023

Front. Pharmacol.

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Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered a “multisystem” disease that simultaneously suffers from metabolic diseases and hepatic steatosis. Some may develop into liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Given the close connection between metabolic diseases and fatty liver, it is urgent to identify drugs that can control metabolic diseases and fatty liver as a whole and delay disease progression. Ferroptosis, characterized by iron overload and lipid peroxidation resulting from abnormal iron metabolism, is a programmed cell death mechanism. It is an important pathogenic mechanism in metabolic diseases or fatty liver, and may become a key direction for improving MASLD. In this article, we have summarized the physiological and pathological mechanisms of iron metabolism and ferroptosis, as well as the connections established between metabolic diseases and fatty liver through ferroptosis. We have also summarized MASLD therapeutic drugs and potential active substances targeting ferroptosis, in order to provide readers with new insights. At the same time, in future clinical trials involving subjects with MASLD (especially with the intervention of the therapeutic drugs), the detection of serum iron metabolism levels and ferroptosis markers in patients should be increased to further explore the efficacy of potential drugs on ferroptosis.

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“…The molecular targets of metformin have been expanded upon in the recent decades ( Foretz et al, 2019 ; Lu et al, 2021 ; Wu et al, 2023 ) but the primary mechanism of this biguanide remains unclear. The activation of adenosine 5’-monophosphate activated protein kinase (AMPK) is considered a core mechanism of metformin; AMPK phosphorylates several key enzymes that regulate the activity of transcription factors, coactivators, and corepressors, thus regulating lipid metabolism, inflammation, autophagy, and gluconeogenesis ( Wang et al, 2019a ; Yang et al, 2019 ; Zhang et al, 2022a ; Li et al, 2022 ; Yang et al, 2022 ) ( Figure 1 ).…”

Section: Molecular Pathway For the Anti-diabetic Effects Of Metforminmentioning

confidence: 99%

The anti-diabetic effects of metformin are mediated by regulating long non-coding RNA

Chang,

Li,

2023

Front. Pharmacol.

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Type 2 diabetes (T2D) is a metabolic disease with complex etiology and mechanisms. Long non-coding ribonucleic acid (LncRNA) is a novel class of functional long RNA molecules that regulate multiple biological functions through various mechanisms. Studies in the past decade have shown that lncRNAs may play an important role in regulating insulin resistance and the progression of T2D. As a widely used biguanide drug, metformin has been used for glucose lowering effects in clinical practice for more than 60 years. For diabetic therapy, metformin reduces glucose absorption from the intestines, lowers hepatic gluconeogenesis, reduces inflammation, and improves insulin sensitivity. However, despite being widely used as the first-line oral antidiabetic drug, its mechanism of action remains largely elusive. Currently, an increasing number of studies have demonstrated that the anti-diabetic effects of metformin were mediated by the regulation of lncRNAs. Metformin-regulated lncRNAs have been shown to participate in the inhibition of gluconeogenesis, regulation of lipid metabolism, and be anti-inflammatory. Thus, this review focuses on the mechanisms of action of metformin in regulating lncRNAs in diabetes, including pathways altered by metformin via targeting lncRNAs, and the potential targets of metformin through modulation of lncRNAs. Knowledge of the mechanisms of lncRNA modulation by metformin in diabetes will aid the development of new therapeutic drugs for T2D in the future.

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Metformin ameliorates ferroptosis in cardiac ischemia and reperfusion by reducing NOX4 expression via promoting AMPKα

Cited by 11 publications

References 27 publications

Effects of Trehalose Preconditioning on H9C2 Cell Viability and Autophagy Activation in a Model of Donation after Circulatory Death for Heart Transplantation

Effects of Trehalose Preconditioning on H9C2 Cell Viability and Autophagy Activation in a Model of Donation after Circulatory Death for Heart Transplantation

Metabolic dysfunction-associated steatotic liver disease: ferroptosis related mechanisms and potential drugs

The anti-diabetic effects of metformin are mediated by regulating long non-coding RNA

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