Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107258 - 107258

Published: June 21, 2024

Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation as hallmarks contributing to vascular damage abnormal cardiac function. Meanwhile, these three novel forms dysfunction closely related mitochondrial homeostasis. Mitochondria the main organelles that supply energy maintain Mitochondrial stability is maintained through a series regulatory pathways, such fission, fusion mitophagy. Studies have shown (e.g., impaired dynamics mitophagy) promotes ROS production, leading oxidative stress, which induces M1 phenotypic polarisation. Therefore, an in-depth knowledge dynamic regulation mitochondria during necessary understand disease development. This paper systematically summarises impact changes in mitophagy on regulating dysfunctions promote understanding pathogenesis diseases provide corresponding theoretical references for treating diseases.

Language: Английский

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Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

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Potential mechanism of dietary palm kernel meal effect on muscle tenderness in Tibetan sheep revealed by proteomics and phosphorylated proteomics

Food Chemistry, Journal Year: 2025, Volume and Issue: 478, P. 143668 - 143668

Published: March 7, 2025

The labe free proteomics technology and 4D phosphorylation was used to systematically analyse the protein expression regulatory mechanisms of muscle tenderness. 59 differentially expressed proteins were screened by proteomic data analysis. Phosphorylated analysis showed 681 modified peptide levels changed, which 235 corresponded 132 up-regulated 446 253 down-regulated. Then, two-omics further predicted that mechanism tenderness mainly based on glycolysis, regulating mitochondrial autophagy, apoptosis, AMPK HIF-1 signaling pathway regulate tenderness, specifically manifested in modulation Ca2+ release promote degradation myofibrillar fibrillar relevant proteins, shortening post-slaughter glycolysis reducing degree glycolysis. Which verified WB, P53, ENO5, ALDOA, ENDOG PINK1 identified as potential factors for regulation.

Language: Английский

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The Dual Role of Exogenous Hydrogen Sulfide (H2S) in Intestinal Barrier Mitochondrial Function: Insights into Cytoprotection and Cytotoxicity Under Non-Stressed Conditions

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 384 - 384

Published: March 25, 2025

Hydrogen sulfide (H2S) is a critical gasotransmitter that plays dual role in physiological and pathological processes, particularly the gastrointestinal tract. While levels of H2S exert cytoprotective effects, excessive concentrations can lead to toxicity, oxidative stress, inflammation. The aim this study was investigate dose-dependent effects exogenous on mitochondrial functions biogenesis intestinal epithelial cells under non-stressed conditions. Using Caco-2 monolayer model, we evaluated impact sodium hydrosulfide (NaHS) at ranging from 1 × 10−7 M 5 10−3 metabolism, redox balance, antioxidant defense, inflammatory responses, autophagy/mitophagy, apoptosis. Our results demonstrated biphasic response: low-to-moderate (1 M–1.5 M) enhance through PGC-1α activation, upregulating TFAM COX-4 expression, increasing mtDNA copy number. In contrast, higher (2 10−3–5 impair function, induce promote These are associated with elevated reactive oxygen species (ROS) production, dysregulation enzymes, COX-2-mediated H2S-induced autophagy/mitophagy protective mechanism intermediate but fails mitigate damage toxic levels. This underscores delicate balance between cytotoxic cells, helping develop new therapeutic approaches for disorders.

Language: Английский

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Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK‐ULK1‐FUNDC1 Signaling Pathway

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

ABSTRACT Osteosarcoma (OS) is the most common primary bone malignancy. The therapeutic efficacy for OS patients has remained stagnant in recent decades. Xanthohumol (XN), a flavonoid naturally found hops, demonstrated significant anticancer properties lung and breast cancer. However, its effect on underlying molecular mechanisms remains uncertain. Therefore, purpose of this study to explore relationship between XN OS. Firstly, we assessed impact cell proliferation migration using CCK‐8, wound‐healing, transwell, clonogenicity assays. Subsequently, examined mitophagy cells through flow cytometry, immunofluorescence, transmission electron microscopy, western blot analysis. Finally, constructed siRNA targeting AMPK validate pathway. In vitro, that inhibited concentration‐ time‐dependent manner. Furthermore, induced mitochondrial damage increased reactive oxygen species (ROS) levels. RNA‐seq analysis suggested potential pathway, which confirmed experimentally by showing reduced ATP levels, altered membrane potential, expression Atg5, Beclin‐1, LC3 proteins. Interestingly, inhibitor Mdivi‐1 reversed caused cells. exerted anti‐OS effects activation AMPK‐ULK1‐FUNDC1 signaling was effectively after knockdown. vivo, subcutaneous nude mouse model without any organ toxicity. emerges as promising pharmaceutical agent

Language: Английский

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Mechanisms underlying targeted mitochondrial therapy for programmed cardiac cell death

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Heart diseases are common clinical diseases, such as cardiac fibrosis, heart failure, hypertension and arrhythmia. Globally, the incidence rate mortality of increasing by years. The main mechanism disease is related to cellular state. Mitochondrion organ energy supply, participating in various signal transduction pathways playing a vital role occurrence development disease. This review summarizes cell death patterns molecular mechanisms associated with mitochondrial dysfunction.

Language: Английский

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Mechanism of Nano‐Microplastics Exposure‐Induced Myocardial Fibrosis: DKK3‐Mediated Mitophagy Dysfunction and Pyroptosis

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(5)

Published: April 22, 2025

ABSTRACT Nano‐microplastics (NMPs), as environmental pollutants, are widely present in nature and pose potential threats to biological health. This study aims investigate the mechanisms by which NMPs inhibit mitophagy through suppression of dickkopf‐related protein 3 (DKK3) expression, leading NOD‐like receptor family, pyrin domain containing (NLRP3) inflammasome‐mediated cardiomyocyte pyroptosis promoting myocardial fibrosis. Healthy adult male C57BL/6 mice were administered NMP solution via gavage, their cardiac function was monitored. The results showed that exposure significantly reduced left ventricular ejection fraction (LVEF) fractional shortening (LVFS) increased extent Transcriptome sequencing identified 14 differentially expressed genes (DEGs), including MYL7. Using random forest algorithm functional enrichment analysis, DKK3 a key gene. In Vitro experiments further confirmed downregulate thereby inhibiting pyroptosis. elucidates molecular induce fibrosis provides new theoretical bases targets for diagnosis treatment heart diseases.

Language: Английский

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Overview of pyroptosis mechanism and in-depth analysis of cardiomyocyte pyroptosis mediated by NF-κB pathway in heart failure

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117367 - 117367

Published: Aug. 29, 2024

The pyroptosis of cardiomyocytes has become an essential topic in heart failure research. abnormal accumulation these biological factors, including angiotensin II, advanced glycation end products, and various growth factors (such as connective tissue factor, vascular endothelial transforming factor beta, among others), activates the nuclear factor-κB (NF-κB) signaling pathway cardiovascular diseases, ultimately leading to cardiomyocytes. Therefore, exploring underlying molecular mechanisms is for developing novel drugs therapeutic strategies. However, our current understanding precise regulatory mechanism this complex cardiomyocyte still limited. Given this, study reviews milestone discoveries field research since 1986, analyzes detail similarities, differences, interactions between other cell death modes apoptosis, necroptosis, autophagy, ferroptosis), explores deep connection failure. At same time, it depicts complete activation, transmission, eventual NF-κB process In addition, also systematically summarizes approaches that can inhibit reduce pyroptosis, drugs, natural compounds, small molecule inhibitors, gene editing, cutting-edge technologies, aiming provide solid scientific support new perspectives prevention treatment

Language: Английский

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