The mechanism of HMGB1 secretion and release

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(2), P. 91 - 102

Published: Feb. 1, 2022

Abstract High mobility group box 1 (HMGB1) is a nonhistone nuclear protein that has multiple functions according to its subcellular location. In the nucleus, HMGB1 DNA chaperone maintains structure and function of chromosomes. cytoplasm, can promote autophagy by binding BECN1 protein. After active secretion or passive release, extracellular usually acts as damage-associated molecular pattern (DAMP) molecule, regulating inflammation immune responses through different receptors direct uptake. The release fine-tuned variety factors, including posttranslational modification (e.g., acetylation, ADP-ribosylation, phosphorylation, methylation) machinery cell death apoptosis, pyroptosis, necroptosis, alkaliptosis, ferroptosis). this minireview, we introduce basic focus on regulatory mechanism release. Understanding these topics may help us develop new HMGB1-targeted drugs for various conditions, especially inflammatory diseases tissue damage.

Language: Английский

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Signaling pathways and defense mechanisms of ferroptosis

FEBS Journal, Journal Year: 2021, Volume and Issue: 289(22), P. 7038 - 7050

Published: June 6, 2021

As a type of lytic cell death driven by unrestricted lipid peroxidation and subsequent plasma membrane damage, ferroptosis occurs develops because sophisticated signals regulatory mechanisms. The reactive oxygen species (ROS) used to initiate come from variety sources, including iron‐mediated Fenton reactions, mitochondrial ROS, membrane‐associated ROS the NOX protein family. Polyunsaturated fatty acid‐containing phospholipids are main substrates in ferroptosis, which is positively regulated enzymes, such as ACSL4, LPCAT3, ALOXs, or POR. Selective activation autophagic degradation pathways promotes increasing iron accumulation cause peroxidation. In contrast, system xc – ‐glutathione–GPX4 axis plays central role limiting peroxidation, although other antioxidants (such coenzyme Q10 tetrahydrobiopterin) can also inhibit ferroptosis. A nuclear mechanism defense against NFE2L2‐dependent antioxidant response transcriptionally upregulating expression cytoprotective genes. Additionally, damage caused ferroptotic stimulus be repaired ESCRT‐III‐dependent scission machinery. this review, we summarize recent progress understanding signaling mechanisms

Language: Английский

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Copper metabolism in cell death and autophagy

Autophagy, Journal Year: 2023, Volume and Issue: 19(8), P. 2175 - 2195

Published: April 14, 2023

Copper is an essential trace element in biological systems, maintaining the activity of enzymes and function transcription factors. However, at high concentrations, copper ions show increased toxicity by inducing regulated cell death, such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis. Furthermore, can trigger macroautophagy/autophagy, a lysosome-dependent degradation pathway that plays dual role regulating survival or death fate cells under various stress conditions. Pathologically, impaired metabolism due to environmental genetic causes implicated variety human diseases, rare Wilson disease common cancers. Therapeutically, copper-based compounds are potential chemotherapeutic agents be used alone combination with other drugs approaches treat cancer. Here, we review progress made understanding metabolic processes their impact on regulation autophagy. This knowledge may help design future clinical tools improve cancer diagnosis treatment.

Language: Английский

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Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells

Autophagy, Journal Year: 2021, Volume and Issue: 17(12), P. 4266 - 4285

Published: April 12, 2021

Zinc oxide nanoparticles (ZnONPs) hold great promise for biomedical applications. Previous studies have revealed that ZnONPs exposure can induce toxicity in endothelial cells, but the underlying mechanisms not been fully elucidated. In this study, we report ferroptosis of both HUVECs and EA.hy926 as evidenced by elevation intracellular iron levels, lipid peroxidation cell death a dose- time-dependent manner. addition, reactive oxygen species (ROS) scavenger ferrostatin-1 chelator deferiprone attenuated ZnONPs-induced death. Intriguingly, found is macroautophagy/autophagy-dependent, because inhibition autophagy with pharmacological inhibitor or ATG5 gene knockout profoundly mitigated ferroptosis. We further demonstrated NCOA4 (nuclear receptor coactivator 4)-mediated ferritinophagy (autophagic degradation major storage protein ferritin) was required induced ZnONPs, showing knockdown reduce level peroxidation, subsequently alleviate Furthermore, showed ROS originating from mitochondria (mtROS) probably activated AMPK-ULK1 axis to trigger ferritinophagy. Most importantly, pulmonary caused vascular inflammation mice, supplementation significantly reversed injury exposure. Overall, our study indicates novel mechanism cytotoxicity, NCOA4-mediated ferroptotic

Language: Английский

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Organelle-specific regulation of ferroptosis

Cell Death and Differentiation, Journal Year: 2021, Volume and Issue: 28(10), P. 2843 - 2856

Published: Aug. 31, 2021

Language: Английский

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Cell death in pancreatic cancer: from pathogenesis to therapy

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 18(11), P. 804 - 823

Published: July 30, 2021

Language: Английский

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GPX4 in cell death, autophagy, and disease

Autophagy, Journal Year: 2023, Volume and Issue: 19(10), P. 2621 - 2638

Published: June 4, 2023

Selenoprotein GPX4 (glutathione peroxidase 4), originally known as PHGPX (phospholipid hydroperoxide glutathione peroxidase), is the main oxidoreductase in use of a reducing agent scavenging lipid peroxidation products. There are three isoforms: cytosolic (cGPX4), mitochondrial (mGPX4), and nuclear (nGPX4), with distinct spatiotemporal expression patterns during embryonic development adult life. In addition to inducing phenotype ferroptosis, loss can some cells trigger apoptosis, necroptosis, pyroptosis, or parthanatos, which mediates accelerates developmental defects, tissue damage, sterile inflammation. The interaction autophagic degradation pathway further modulates cell fate response oxidative stress. Impaired function implicated tumorigenesis, neurodegeneration, infertility, inflammation, immune disorders, ischemia-reperfusion injury. Additionally, R152H mutation promote Sedaghatian-type spinal metaphyseal dysplasia, rare fatal disease newborns. Here, we discuss roles classical functions well emerging GPX4-regulated processes death, autophagy, disease.Abbreviations: AA: arachidonic acid; cGPX4: GPX4; CMA: chaperone-mediated autophagy; DAMPs: danger/damage-associated molecular patterns; mGPX4: nGPX4: GSDMD-N: N-terminal fragment GSDMD; I/R: ischemia-reperfusion; PLOOH: phospholipid hydroperoxide; PUFAs: polyunsaturated fatty acids; RCD: regulated death; ROS: reactive oxygen species; Se: selenium; SSMD: spondylometaphyseal dysplasia; UPS: ubiquitin-proteasome system

Language: Английский

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GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(3), P. 188890 - 188890

Published: March 29, 2023

Language: Английский

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Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(11)

Published: Oct. 29, 2021

Abstract Ferroptosis is a form of regulated cell death that emerges to be relevant for therapy-resistant and dedifferentiating cancers. Although several lines evidence suggest ferroptosis type autophagy-dependent death, the underlying molecular mechanisms remain unclear. Fin56, 3 inducer, triggers by promoting glutathione peroxidase 4 (GPX4) protein degradation via not fully understood pathway. Here, we determined Fin56 induces autophagy in bladder cancer cells Fin56-triggered mechanistically depends on autophagic machinery. Furthermore, found inhibition at different stages attenuates Fin56-induced oxidative stress GPX4 degradation. Moreover, investigated effects combination with Torin 2, potent mTOR inhibitor used activate autophagy, viability. We synergizes 2 cytotoxicity against cells. Collectively, our findings only support concept but imply combined application inducers inhibitors promising approach improve therapeutic options treatment cancer.

Language: Английский

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Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity

ACS Nano, Journal Year: 2022, Volume and Issue: 16(6), P. 9228 - 9239

Published: May 27, 2022

Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from resources, especially daily food, implies a promising direction for exploring treatment strategies human diseases. Here, we report biocompatible nanozyme prepared chlorogenic acid (ChA), major bioactive product coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation GPX4-catalyzed lipid repair systems. In vivo, dramatically suppressed the tumor growth in HepG2-tumor-bearing mice negligible side toxicity. Particularly, hepatoma H22-bearing mice, recruited massive tumor-infiltrating immune cells including T cells, NK macrophages, thereby converting "cold" "hot" tumors activating systemic antitumor responses. Taken together, our study suggests product-derived coffee can serve biologically safe anticancer therapeutics may aid development nanotechnology-based immunotherapeutic.

Language: Английский

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