The emerging role of nuclear receptor coactivator 4 in health and disease: a novel bridge between iron metabolism and immunity DOI Creative Commons
Yue Le, Qinjie Liu, Yi Yang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 3, 2024

Nuclear receptor coactivator 4 (NCOA4) has recently been recognized as a selective cargo of ferritinophagy participating in ferroptosis. However, NCOA4 is also that modulates the transcriptional activity many vital nuclear receptors. Recent novel studies have documented role healthy and pathogenic conditions via its modulation iron- non-iron-dependent metabolic pathways. exhibits non-ferritinophagic iron-independent features such promoting tumorigenesis erythropoiesis, immunomodulation, regulating autophagy, DNA replication mitosis. Full-length human-NCOA4 composed 614 amino acids, which N-terminal (1-237) contains nuclear-receptor-binding domains, while C-terminal (238-614) principally ferritin-binding domain. The exploration protein structure suggests possesses additional significant complex functions based on structural domains. Intriguingly, another three isoforms are produced by alternative splicing identified, may display disparate activities physiological pathological processes. Thus, become an important bridge encompasses interactions between immunity metabolism. In this review, we outline latest advances mechanisms underlying actions health disease conditions, providing insights into potential therapeutic interventions.

Language: Английский

Curcumol: a review of its pharmacology, pharmacokinetics, drug delivery systems, structure–activity relationships, and potential applications DOI

Sicheng Zhai,

Rui Wang, Jingyuan Wang

et al.

Inflammopharmacology, Journal Year: 2024, Volume and Issue: 32(3), P. 1659 - 1704

Published: March 23, 2024

Language: Английский

Citations

9
Regulation of Hippo-YAP1/TAZ pathway in metabolic dysfunction-associated steatotic liver disease DOI Creative Commons

Wei Xuan,

Dandan Song, Jianhua Hou

et al.

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

Published: Jan. 23, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic worldwide, but effective treatments are still lacking. disorders such as iron overload, glycolysis, insulin resistance, lipid dysregulation, and glutaminolysis found to induce senescence ferroptosis, which hot topics in research of MASLD. Recent studies have shown that Hippo–YAP1/TAZ pathway is involved regulations metabolism disorders, senescence, inflammation, fibrosis MASLD, their complex connections contrast roles also reported. In addition, therapeutics based on hold promising for MASLD treatment. this review, we highlight regulation molecular mechanism summarize potential therapeutic strategies by regulating pathway.

Language: Английский

Citations

1
Ferritinophagy: multifaceted roles and potential therapeutic strategies in liver diseases DOI Creative Commons

Kejia Wu,

Wei Zhao,

Zeyu Hou

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 25, 2025

Ferritinophagy, the selective autophagic degradation of ferritin to release iron, is emerging as a critical regulator iron homeostasis and key player in pathogenesis various liver diseases. This review comprehensively examines mechanisms, regulation, multifaceted roles ferritinophagy health disease. Ferritinophagy intricately regulated by several factors, including Nuclear Receptor Coactivator 4 (NCOA4), Iron regulatory proteins signaling pathways such mTOR AMPK. These mechanisms ensure proper utilization prevent overload, which can induce oxidative stress ferroptosis. In diseases, exhibits dual roles. fibrosis, promoting hepatic stellate cells (HSCs) cell senescence reduce fibrosis progression. However, non-alcoholic fatty disease (NAFLD), chronic may exacerbate injury through overload stress. hepatocellular carcinoma (HCC), be harnessed novel therapeutic strategy inducing ferroptosis cancer cells. Additionally, implicated drug-induced sepsis-associated damage, highlighting its broad impact on pathology. also explores crosstalk between other autophagy pathways, mitophagy lipophagy, collectively influence cellular Understanding these interactions essential for developing comprehensive strategies targeting multiple pathways. summary, complex dynamic process with significant implications provides an in-depth analysis ferritinophagy's potential target, emphasizing need further research elucidate role

Language: Английский

Citations

1
Terpenoids: Natural Compounds for Non-Alcoholic Fatty Liver Disease (NAFLD) Therapy DOI Creative Commons

Pengyu Yao,

Yajuan Liu

Molecules, Journal Year: 2022, Volume and Issue: 28(1), P. 272 - 272

Published: Dec. 29, 2022

Natural products have been the most productive source for development of drugs. Terpenoids are a class natural active with wide range pharmacological activities and therapeutic effects, which can be used to treat variety diseases. Non-alcoholic fatty liver disease (NAFLD), common metabolic disorder worldwide, results in health burden economic problems. A literature search was conducted obtain information relevant treatment NAFLD terpenoids using electronic databases, namely PubMed, Web Science, Science Direct, Springer, period 2011-2021. In total, we found 43 NAFLD. Over dozen terpenoid compounds origin were classified into five categories according their structure: monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, tetraterpenoids. We that play role NAFLD, mainly by regulating lipid metabolism disorder, insulin resistance, oxidative stress, inflammation. The AMPK, PPARs, Nrf-2, SIRT 1 pathways main targets treatment. promising drugs will potentially create more opportunities However, current studies restricted animal cell experiments, lack clinical research systematic structure-activity relationship (SAR) studies. future, should further enrich on mechanism terpenoids, carry out SAR research, increase likelihood breakthrough insights field.

Language: Английский

Citations

37
Curcumol alleviates liver fibrosis through inducing autophagy and ferroptosis in hepatic stellate cells DOI
Yang Zheng, Tiejian Zhao,

Jiaru Wang

et al.

The FASEB Journal, Journal Year: 2022, Volume and Issue: 36(12)

Published: Nov. 18, 2022

To explore the effect of curcumol on autophagy and ferroptosis hepatic stellate cells, to clarify molecular mechanism its anti-hepatic fibrosis. In present study, we report that promotes death activated HSCs reduces deposition extracellular matrix. Interestingly, treatment can trigger eliminate characterized by iron overload, lipid ROS accumulation, glutathione depletion, peroxidation. Curcumol HSC autophagy, which may be key for induction ferroptosis. It is worth noting upregulation nuclear receptor coactivator 4 (NCOA4) play a mechanism. NCOA4 mediates release ions induces occurrence Overall, in degradation FTH1 complexes, releases ions, leads ferroptosis, an important fibrosis effect.

Language: Английский

Citations

34
High-Dose Ionizing Radiation Accelerates Atherosclerotic Plaque Progression by Regulating P38/NCOA4-Mediated Ferritinophagy/Ferroptosis of Endothelial Cells DOI

Zhinan Wu,

Taiwei Chen, Yuxuan Qian

et al.

International Journal of Radiation Oncology*Biology*Physics, Journal Year: 2023, Volume and Issue: 117(1), P. 223 - 236

Published: April 12, 2023

Language: Английский

Citations

22
Schisandrin B promotes senescence of activated hepatic stellate cell via NCOA4-mediated ferritinophagy DOI Creative Commons
Mingyue Ma, Na Wei,

Yang Jie-ren

et al.

Pharmaceutical Biology, Journal Year: 2023, Volume and Issue: 61(1), P. 621 - 629

Published: April 3, 2023

Schisandrin B (Sch B), an active ingredient from Schisandrae chinensis (Turcz.) Baill. (Schisandraceae) Fructus, possesses diverse pharmacological activities including antitumor, anti-inflammation, and hepatoprotection.To explore the effect of Sch on activated HSCs senescence in hepatic fibrosis mechanisms implicated.ICR mice with CCl4-induced were supplemented (40 mg/kg) for 30 d LX2 cells treated (5, 10 20 μM) 24 h. Cellular was assessed by senescence-related indicators senescence-associated β-galactosidase (SA-β-gal) activity expression p16, p21, p53, γ-H2AX, H3K9me3, TERT, TRF1, TRF2. Ferric ammonium citrate (FAC) NCOA4 siRNA used to evaluate underlying B's regulation cellular senescence.Sch reduced serum levels AST ALT (53.2% 63.6%), alleviated collagen deposition, promoted mice. Treatment (20 decreased cell viability 80.38 ± 4.87% elevated SA-β-gal activity, p21 p53 increased 4.5-, 2.9-, 3.5-fold TRF1 TRF2 2.4-, 2.7-, 2.6-fold cells. FAC (400 enhanced mentioned above. weakened effects iron deposition could ameliorate through promotion senescence, which might be attributed its induction NCOA4-mediated ferritinophagy subsequent overload.

Language: Английский

Citations

20
Ferritinophagy in the etiopathogenic mechanism of related diseases DOI Open Access
Xuemei Jin, Chunjie Jiang,

Zhizhou Zou

et al.

The Journal of Nutritional Biochemistry, Journal Year: 2023, Volume and Issue: 117, P. 109339 - 109339

Published: April 13, 2023

Language: Английский

Citations

20
The role of ferroptosis in metabolic diseases DOI Creative Commons
Ling Xie, Bin Fang, Chun Zhang

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2023, Volume and Issue: 1870(6), P. 119480 - 119480

Published: April 30, 2023

Language: Английский

Citations

18
PDK4 rescues high-glucose-induced senescent fibroblasts and promotes diabetic wound healing through enhancing glycolysis and regulating YAP and JNK pathway DOI Creative Commons
Zhouji Ma, Youjun Ding, Xiaofeng Ding

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Nov. 25, 2023

During the process of wound healing, fibroblasts migrate to site and perform essential functions in promoting cell proliferation, as well synthesizing secreting extracellular matrix (ECM). However, diabetic wounds, senescent exhibit impaired proliferative capacity fail synthesize ECM components. Pyruvate dehydrogenase kinase 4 (PDK4), a key enzyme regulating energy metabolism, has been implicated modulating cellular senescence fibroblast function. its specific role wounds remains poorly understood. In this study, we conducted series vivo vitro experiments using STZ-induced mice human dermal fibroblasts. We evaluated markers, including SA-β-gal, P53, P16, P21, PAI-1, senescence-associated secretory phenotype (SASP) factors. Finally, observed that PDK4 increased normal but expression was insufficient wounds. Significantly, overexpression demonstrated potential accelerate healing improve both vitro. Furthermore, our study elucidated underlying mechanism by which improved through enhancement glycolysis regulation YAP JNK pathway. The effect dependent on metabolic reprogramming subsequent reduction reactive oxygen species (ROS), mediated PDK4. Overall, findings highlight promising therapeutic target for addressing

Language: Английский

Citations

17