The redox protein HMGB1 in cell death and cancer DOI
Ruochan Chen, Ju Zou, Rui Kang

et al.

Antioxidants and Redox Signaling, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 2, 2023

Significance: As a redox-sensitive protein, high-mobility group box 1 (HMGB1) is implicated in regulating stress responses to oxidative damage and cell death, which are closely related the pathology of inflammatory diseases, including cancer. Recent advances: HMGB1 non-histone nuclear protein that acts as DNA chaperone control chromosomal structure function. can also be released into extracellular space function damage-associated molecular pattern during apoptosis, necrosis, necroptosis, pyroptosis, ferroptosis, alkaliptosis, cuproptosis. Once released, binds membrane receptors shape immune metabolic responses. In addition subcellular localization, activity depends on its redox state posttranslational modifications. Abnormal plays dual role tumorigenesis anticancer therapy (e.g., chemotherapy, radiation therapy, immunotherapy) depending tumor types stages. Critical issues: A comprehensive understanding cellular homeostasis important for deciphering normal functions pathological manifestations. this review, we discuss compartmental-defined roles death Understanding these advances may help us develop potential HMGB1-targeting drugs or approaches treat stress-related diseases conditions. Future directions: Further studies required dissect mechanism by maintains under different multidisciplinary effort evaluate applications precisely targeting pathway human health disease.

Language: Английский

Copper metabolism in cell death and autophagy DOI Creative Commons
Qian‐Li Xue, Rui Kang, Daniel J. Klionsky

et al.

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

Citations

299
GPX4 in cell death, autophagy, and disease DOI Creative Commons
Yangchun Xie, Rui Kang, Daniel J. Klionsky

et al.

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

Citations

230
The pyroptotic role of Caspase-3/GSDME signalling pathway among various cancer: A Review DOI
Asif Ahmad Bhat, Riya Thapa, Obaid Afzal

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 242, P. 124832 - 124832

Published: May 15, 2023

Language: Английский

Citations

100
Pyroptosis in inflammation-related respiratory disease DOI Creative Commons

Yuanyu Feng,

Min Li,

Xiaoting Yangzhong

et al.

Journal of Physiology and Biochemistry, Journal Year: 2022, Volume and Issue: 78(4), P. 721 - 737

Published: July 11, 2022

Abstract Pyroptosis is commonly induced by the gasdermin (GSDM) family and accompanied release of inflammatory cytokines such as IL-1β IL-18. Recently, increasing evidence suggests that pyroptosis plays a role in respiratory diseases. This review aimed to summarize roles mechanisms inflammation-related There are several pathways involved pyroptosis, canonical inflammasome-induced pathway, non-canonical caspase-1/3/6/7/GSDMB caspase-8/GSDMC caspase-8/GSDMD caspase-3/GSEME pathway. may be asthma, chronic obstructive pulmonary disease (COPD), lung cancer, acute injury (ALI), silicosis, hypertension (PH), tuberculosis (TB), which NLRP3 pathway mostly highlighted. contributes deterioration COPD, ALI, PH. In addition, has dual effects on cancer TB. Additionally, whether participates cystic fibrosis (CF) sarcoidosis or not largely unknown, though activation inflammasome found CF sarcoidosis. conclusion, play diseases, providing new therapeutic targets.

Language: Английский

Citations

93
Pyroptosis and pyroptosis-inducing cancer drugs DOI Open Access
Fan Yang, Sahana Bettadapura, Mark S. Smeltzer

et al.

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 43(10), P. 2462 - 2473

Published: March 14, 2022

Language: Английский

Citations

87
TNF-α contributes to sarcopenia through caspase-8/caspase-3/GSDME-mediated pyroptosis DOI Creative Commons
Jingying Wu, Siming Lin,

Weixiao Chen

et al.

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

Published: Feb. 24, 2023

Abstract Sarcopenia has become a leading cause of disability and mortality in the elderly. It been reported that programmed cell death (PCD) is associated with development sarcopenia characterized by reduction muscle fiber size number. TNF-α also validated to play prominent role through its complex signaling pathways including signaling. However, it still unclear whether contributes mediating pyroptosis, one type PCD. Here, we first established naturally aged mice model confirmed an inflammatory state represented mice. Evidence GSDME-mediated pyroptosis activation apoptotic caspase-8/-3 were found skeletal cells sarcopenia. We demonstrated triggered myotubes activating caspase-8 caspase-3 using inhibitors. Comparing GSDME expression between TNF Complex IIa IIb, was be more inclined assemble IIb triggering pyroptosis. Moreover, pyroptotic result decreased MHC1 finally loss knockdown GSDME. Our work reveals novel mechanism TNF-ɑ/caspase-8/caspase-3/GSDME signaling-mediated Caspase-3/GSDME may promising therapeutic target for

Language: Английский

Citations

42
Pyroptosis in health and disease: mechanisms, regulation and clinical perspective DOI Creative Commons
Yifan Liu,

Renjie Pan,

Yuzhen Ouyang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

Citations

37
Role of pyroptosis in the pathogenesis of various neurological diseases DOI
Abiola Oladapo,

Thomas L. Jackson,

Jueliet Menolascino

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 428 - 446

Published: Feb. 7, 2024

Language: Английский

Citations

29
The gasdermin family: emerging therapeutic targets in diseases DOI Creative Commons
Cheng‐long Zhu, Sheng Xu, Ruoyu Jiang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 7, 2024

Abstract The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player pyroptosis. This recently characterized class of pore-forming effector proteins is orchestrating processes such membrane permeabilization, pyroptosis, the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants infections. GSDMs have been implicated range diseases including, but not limited to, sepsis, viral infections, cancer, either through involvement pyroptosis or independently this process. regulation GSDM-mediated gaining recognition promising therapeutic strategy treatment various diseases. Current strategies inhibiting GSDMD primarily involve binding to GSDMD, blocking cleavage GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In review, we delve into cutting-edge understanding interplay between elucidate activation GSDMs, explore their associations diseases, discuss recent advancements potential developing inhibitors.

Language: Английский

Citations

24
Apoptosis in Cancer Biology and Therapy DOI
Allison Moyer, Kosuke Tanaka, Emily H. Cheng

et al.

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2025, Volume and Issue: 20(1), P. 303 - 328

Published: Jan. 24, 2025

Since its inception, the study of apoptosis has been intricately linked to field cancer. The term was coined more than five decades ago following identification in both healthy tissues and malignant neoplasms. subsequent elucidation molecular mechanisms significantly enhanced our understanding how cancer cells hijack physiological processes evade cell death. Moreover, it shed light on pathways through which most anticancer therapeutics induce tumor death, including targeted therapy immunotherapy. These mechanistic studies have paved way for development directly targeting either pro- or antiapoptotic proteins. Notably, US Food Drug Administration (FDA) approved BCL-2 inhibitor venetoclax 2016, with additional agents currently undergoing clinical trials. Recent research brought forefront anti- proinflammatory effects individual apoptotic pathways. This underscores ongoing imperative deepen comprehension apoptosis, particularly as we navigate evolving landscape

Language: Английский

Citations

3