Iron metabolism and ferroptosis in type 2 diabetes mellitus and complications: mechanisms and therapeutic opportunities

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 8, 2023

Abstract The maintenance of iron homeostasis is essential for proper endocrine function. A growing body evidence suggests that imbalance a key factor in the development several diseases. Nowadays, ferroptosis, an iron-dependent form regulated cell death, has become increasingly recognized as important process to mediate pathogenesis and progression type 2 diabetes mellitus (T2DM). It been shown ferroptosis pancreas β cells leads decreased insulin secretion; liver, fat, muscle induces resistance. Understanding mechanisms concerning regulation metabolism T2DM may lead improved disease management. In this review, we summarized connection between metabolic pathways molecular T2DM. Additionally, discuss potential targets treating analysis current limitations future directions these novel treatment targets.

Language: Английский

---

Canagliflozin mitigates ferroptosis and improves myocardial oxidative stress in mice with diabetic cardiomyopathy

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 14, 2022

Canagliflozin (Cana), an anti-diabetes drug belongs to sodium-glucose cotransporter 2 inhibitor, is gaining interest because of its extra cardiovascular benefits. Ferroptosis a new mode cell death, which can promote the occurrence diabetic cardiomyopathy (DCM). Whether Cana alleviate DCM by inhibiting ferroptosis focus this study. Here, we induced models in C57BL6 mice and treated with Cana. Meanwhile, order exclude hypoglycemic effect, high glucose model H9C2 cells were established. In vivo study, observed that could effectively damage cardiac function mice, including increasing lactate dehydrogenase (LDH) troponin I (cTnI), alleviating myocardial fiber breakage, inflammation, collagen deposition mitochondrial structural disorder. We evaluated reactive oxygen species (ROS) levels DCFH-DA BODIPY 581/591 C11, vitro reduced ROS lipid glucose. JC-1 fluorochrome assay showed decreased membrane potential (MMP) was increased Furthermore, inhibitory effects on oxidative stress verified protein carbonyl (PCO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH). As key inducer ferroptosis, total iron Fe 2+ be inhibited both . addition, western blot results indicated expression ferritin heavy-chain (FTN-H) down-regulated, cystine-glutamate antiporter (xCT) up-regulated cells, suggesting inhibit balancing homeostasis promoting system Xc - /GSH/GPX4 axis DCM. These findings underscore fact plays important role development progression targeting may novel strategy for prevention treatment. conclusion, exert some benefits attenuating ferroptosis.

Language: Английский

---

Flexible Self-Powered Sensing System Based on Novel DNA Circuit Strategy and Graphdiyne for Thalassemia Gene by Rapid Naked-Eye Tracking and Open-Circuit Voltage

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(44), P. 16374 - 16382

Published: Oct. 23, 2023

Based on the controllable instantaneous self-assembly ability of long-chain branched DNA nanostructures and synergistic effect between nucleic acid amplification without enzymes, a highly sensitive specific self-powered biosensing platform is developed. Two-dimensional graphdiyne prepared, modified flexible carbon cloth, then functionalized with gold nanoparticles. When mi-tubes are applied it, target thalassemia gene CD122 triggers dual-catalytic hairpin assembly reaction. The generated nanoscale precisely captured by mi-tube, exposing binding sites activating hybridization chain reaction to form DNA. Double-stranded DNA, along dendritic carrying large number guanine bases, captures signal molecule methylene blue (MB), generating significant electrochemical signal. redox MB also causes proportional change in system's color, achieving colorimetric detection functionality. An efficient dual-mode sensing platform, therefore, established for detecting CD122. linear response range concentration open-circuit voltage RGB Blue value 0.0001–10,000 pM. limit under mode 36.3 aM (S/N = 3), mode, it as low 12.1 3). new method exhibits high sensitivity, excellent selectivity, accuracy, providing universal strategy designing novel platforms that can be extended other biomolecules.

Language: Английский

---

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

---

Ferroptosis in health and disease

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103211 - 103211

Published: May 30, 2024

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark ferroptosis uncontrolled overwhelming peroxidation polyunsaturated fatty acids contained membrane phospholipids, which eventually leads to rupture the plasma membrane. unique that it essentially spontaneous, uncatalyzed chemical process based on perturbed iron redox homeostasis contributing process, but nonetheless modulated by many metabolic nodes impinge cells' susceptibility ferroptosis. Among affecting sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets treatment numerous currently incurable diseases. Herein, current members Germany-wide research consortium focusing research, well key external experts who made seminal contributions this rapidly growing exciting field gathered provide comprehensive, state-of-the-art review Specific topics include: basic mechanisms, vivo relevance, specialized methodologies, tools, potential contribution disease etiopathology progression. We hope article will not only established scientists newcomers with an overview multiple facets ferroptosis, also encourage additional efforts characterize further molecular pathways modulating ultimate goal develop novel pharmacotherapies tackle associated - or caused

Language: Английский

---

Dapagliflozin alleviates myocardial ischemia/reperfusion injury by reducing ferroptosis via MAPK signaling inhibition

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 20, 2023

Reperfusion is essential for ischemic myocardium but paradoxically leads to myocardial damage that worsens cardiac functions. Ferroptosis often occurs in cardiomyocytes during ischemia/reperfusion (I/R). The SGLT2 inhibitor dapagliflozin (DAPA) exerts cardioprotective effects independent of hypoglycemia. Here, we investigated the effect and potential mechanism DAPA against injury (MIRI)-related ferroptosis using MIRI rat model hypoxia/reoxygenation (H/R)-induced H9C2 cardiomyocytes. Our results show significantly ameliorated injury, reperfusion arrhythmia, function, as evidenced by alleviated ST-segment elevation, biomarkers including cTnT BNP pathological features, prevented H/R-triggered cell viability loss vitro. In vitro vivo experiments showed inhibited upregulating SLC7A11/GPX4 axis FTH inhibiting ACSL4. notably mitigated oxidative stress, lipid peroxidation, ferrous iron overload, reduced ferroptosis. Subsequently, network pharmacology bioinformatics analysis suggested MAPK signaling pathway was a target common treatment phosphorylation vivo, suggesting might protect reducing through pathway.

Language: Английский

---

Heavy Metal Exposure and Cardiovascular Disease

Circulation Research, Journal Year: 2024, Volume and Issue: 134(9), P. 1160 - 1178

Published: April 25, 2024

Heavy metals are harmful environmental pollutants that have attracted widespread attention due to their health hazards human cardiovascular disease. metals, including lead, cadmium, mercury, arsenic, and chromium, found in various sources such as air, water, soil, food, industrial products. Recent research strongly suggests a connection between disease exposure toxic heavy metals. Epidemiological, basic, clinical studies revealed can promote the production of reactive oxygen species, which then exacerbate species generation induce inflammation, resulting endothelial dysfunction, lipid metabolism distribution, disruption ion homeostasis, epigenetic changes. Over time, metal eventually results an increased risk hypertension, arrhythmia, atherosclerosis. Strengthening public prevention application chelation or antioxidants, vitamins beta-carotene, along with minerals, selenium zinc, diminish burden attributable exposure.

Language: Английский

---

The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

---

Myocardial ischemia/reperfusion: Translational pathophysiology of ischemic heart disease

Med, Journal Year: 2024, Volume and Issue: 5(1), P. 10 - 31

Published: Jan. 1, 2024

Ischemic heart disease is the greatest health burden and most frequent cause of death worldwide. Myocardial ischemia/reperfusion pathophysiological substrate ischemic disease. Improvements in prevention treatment have reduced mortality developed countries over last decades, but further progress now stagnant, morbidity from developing are increasing. Significant problems remain to be resolved require a better understanding. The present review attempts briefly summarize state art myocardial research, with view on both its coronary vascular aspects, define cutting edges where mechanistic knowledge needed facilitate translation clinical practice.

Language: Английский

---

Iron Metabolism in Cardiovascular Disease: Physiology, Mechanisms, and Therapeutic Targets

Circulation Research, Journal Year: 2023, Volume and Issue: 132(3), P. 379 - 396

Published: Feb. 2, 2023

The cardiovascular system requires iron to maintain its high energy demands and metabolic activity. Iron plays a critical role in oxygen transport storage, mitochondrial function, enzyme However, excess is also cardiotoxic due ability catalyze the formation of reactive species promote oxidative damage. While mammalian cells have several redundant import mechanisms, they are equipped with single iron-exporting protein, which makes particularly sensitive overload. As result, levels tightly regulated at many homeostasis. dysregulation ranges from deficiency overload seen types disease, including heart failure, myocardial infarction, anthracycline-induced cardiotoxicity, Friedreich's ataxia. Recently, use intravenous therapy has been advocated patients failure certain criteria for deficiency. Here, we provide an overview systemic cellular homeostasis context physiology, deficiency, current therapeutic strategies, future perspectives.

Language: Английский

---