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Hepatology Communications Aug 2023The role of thioredoxin-interacting protein (TXNIP) in lipopolysaccharide-induced liver injury in mice has been reported, but the underlying mechanisms are poorly...
BACKGROUND
The role of thioredoxin-interacting protein (TXNIP) in lipopolysaccharide-induced liver injury in mice has been reported, but the underlying mechanisms are poorly understood.
METHODS
We overexpressed deubiquitinase in cells overexpressing TXNIP and then detected the level of TXNIP to screen out the deubiquitinase regulating TXNIP; the interaction between TXNIP and deubiquitinase was verified by coimmunoprecipitation. After knockdown of a deubiquitinase and overexpression of TXNIP in Huh7 and HepG2 cells, lipopolysaccharide was used to establish a cellular inflammatory model to explore the role of deubiquitinase and TXNIP in hepatocyte inflammation.
RESULTS
In this study, we discovered that ubiquitin-specific protease 5 (USP5) interacts with TXNIP and stabilizes it through deubiquitylation in Huh-7 and HepG2 cells after treatment with lipopolysaccharide. In lipopolysaccharide-treated Huh-7 and HepG2 cells, USP5 knockdown increased cell viability, reduced apoptosis, and decreased the expression of inflammatory factors, including NLRP3, IL-1β, IL-18, ASC, and procaspase-1. Overexpression of TXNIP reversed the phenotype induced by knockdown USP5.
CONCLUSIONS
In summary, USP5 promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein.
Topics: Apoptosis; Deubiquitinating Enzymes; Lipopolysaccharides; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction; Humans; Hep G2 Cells; Endopeptidases; Carrier Proteins
PubMed: 37534934
DOI: 10.1097/HC9.0000000000000193 -
Molecular Cancer Aug 2023The reversible oxidation-reduction homeostasis mechanism functions as a specific signal transduction system, eliciting related physiological responses. Disruptions to... (Review)
Review
The reversible oxidation-reduction homeostasis mechanism functions as a specific signal transduction system, eliciting related physiological responses. Disruptions to redox homeostasis can have negative consequences, including the potential for cancer development and progression, which are closely linked to a series of redox processes, such as adjustment of reactive oxygen species (ROS) levels and species, changes in antioxidant capacity, and differential effects of ROS on downstream cell fate and immune capacity. The tumor microenvironment (TME) exhibits a complex interplay between immunity and regulatory cell death, especially autophagy and apoptosis, which is crucially regulated by ROS. The present study aims to investigate the mechanism by which multi-source ROS affects apoptosis, autophagy, and the anti-tumor immune response in the TME and the mutual crosstalk between these three processes. Given the intricate role of ROS in controlling cell fate and immunity, we will further examine the relationship between traditional cancer therapy and ROS. It is worth noting that we will discuss some potential ROS-related treatment options for further future studies.
Topics: Humans; Reactive Oxygen Species; Tumor Microenvironment; Oxidation-Reduction; Apoptosis; Autophagy; Neoplasms
PubMed: 37563639
DOI: 10.1186/s12943-023-01831-w -
International Urology and Nephrology May 2024Pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, is thought to be closely associated with the pathogenesis of diseases. Recently, the... (Review)
Review
Pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, is thought to be closely associated with the pathogenesis of diseases. Recently, the association between pyroptosis and urinary diseases has attracted considerable attention, and a comprehensive review focusing on this issue is not available. In this study, we reviewed the role of pyroptosis in the development and progression of benign urinary diseases and urinary malignancies. Based on this, pyroptosis has been implicated in the development of urinary diseases. In summary, this review sheds light on future research directions and provides novel ideas for using pyroptosis as a powerful tool to fight urinary diseases.
Topics: Humans; Pyroptosis; Urogenital Diseases; Apoptosis; Necrosis
PubMed: 38103146
DOI: 10.1007/s11255-023-03894-6 -
European Review For Medical and... Aug 2023Osteoarthritis (OA) is a high-incidence disease of the orthopedic system. However, studies on the molecular mechanisms of OA and pyroptosis, apoptosis, and necroptosis...
OBJECTIVE
Osteoarthritis (OA) is a high-incidence disease of the orthopedic system. However, studies on the molecular mechanisms of OA and pyroptosis, apoptosis, and necroptosis (PANoptosis) at the transcriptome level remain scarce. Therefore, this study purposed to detect biomarkers in OA and explore their relationship to the immune microenvironment.
MATERIALS AND METHODS
OA-related expression data was sourced from the Gene Expression Omnibus (GEO) database. Subsequently, differentially expressed analysis and a Venn diagram were performed to obtain differentially expressed PANoptosis-related genes (DEPGs). Furthermore, the least absolute shrinkage and selection operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and random forest (RF) were implemented to screen diagnostic genes. Receiver operating characteristic (ROC) curves were performed to verify the diagnostic ability of the diagnostic genes. Next, immune infiltration analysis was performed to find the relationships between differential immune cells (OA vs. normal) and diagnostic genes. Finally, drug prediction analysis was also carried out, and the expression of diagnostic genes was verified in external datasets.
RESULTS
A total of 62 DEPGs were identified, which were enriched for regulating apoptotic signaling pathways, tumor necrosis factor (TNF) signaling pathways, and other related pathways. Three feature genes, nuclear factor-kappa-B inhibitor-alpha (NFKBIA), RING finger protein 34 (RNF34), and serine incorporator 3 (SERINC3) were obtained by intersecting genes obtained by the LASSO regression algorithm, SVM algorithm, and RF algorithm and showed excellent diagnostic efficacy with the Area under the curve (AUC) values of individual genes were all greater than 0.7, indicating that the model was more effective. Immuno-infiltration analysis showed that RNF34 was positively correlated with CD56dim natural killer cells, type 17 helper T cells, and NFKBIA was positively correlated with plasmacytoid dendritic cells. Additionally, 12 drugs were predicted by NFKBIA, such as gambogic acid and dioscin. In addition, NFKBIA and SERINC3 were significantly downregulated, and RNF34 was upregulated in OA samples.
CONCLUSIONS
Three genes (NFKBIA, RNF34, and SERINC3) related to PANoptosis, were obtained by bioinformatics analysis, which would provide a new direction for the diagnosis and treatment of OA.
Topics: Pyroptosis; Necroptosis; Apoptosis; Biomarkers; Algorithms
PubMed: 37667921
DOI: 10.26355/eurrev_202308_33396 -
Frontiers in Bioscience (Landmark... Apr 2024Dendritic cells (DCs), the most efficient antigen-presenting cells (APCs), bridge the innate and adaptive immune systems. As such, the turn-over of DCs is critical... (Review)
Review
Dendritic cells (DCs), the most efficient antigen-presenting cells (APCs), bridge the innate and adaptive immune systems. As such, the turn-over of DCs is critical during autoimmune responses, and the dysregulation of DC apoptosis could cause severe immune destruction in the host. For example, reduction of immunogenic DCs by increased apoptosis could lead to immune tolerance to pathogen infection that might allow exposure of nuclear autoantigens, whereas reduced apoptosis could result in long-term lymphocyte activation to break the immune tolerance for the development of autoimmune disease. Thus, keeping a balance between survival and apoptosis of DCs is crucial to maintain immune homeostasis. In this review, we summarize the recent development on the factors inducing DC apoptosis and their underlying mechanisms to provide insights into the immunopathogenesis of some autoimmune diseases, which could lead to effective therapeutic interventions in the clinics.
Topics: Dendritic Cells; Humans; Autoimmune Diseases; Apoptosis; Animals; Immune Tolerance
PubMed: 38682203
DOI: 10.31083/j.fbl2904157 -
Biomedicine & Pharmacotherapy =... Dec 2023Copper-induced cell death, also known as cuproptosis, is distinct from other types of cell death such as apoptosis, necrosis, and ferroptosis. It can trigger the... (Review)
Review
Copper-induced cell death, also known as cuproptosis, is distinct from other types of cell death such as apoptosis, necrosis, and ferroptosis. It can trigger the accumulation of lethal reactive oxygen species, leading to the onset and progression of aging. The significant increases in copper ion levels in the aging populations confirm a close relationship between copper homeostasis and vascular aging. On the other hand, vascular aging is also closely related to the occurrence of various cardiovascular diseases throughout the aging process. However, the specific causes of vascular aging are not clear, and different living environments and stress patterns can lead to individualized vascular aging. By exploring the correlations between copper-induced cell death and vascular aging, we can gain a novel perspective on the pathogenesis of vascular aging and enhance the prognosis of atherosclerosis. This article aims to provide a comprehensive review of the impacts of copper homeostasis on vascular aging, including their effects on endothelial cells, smooth muscle cells, oxidative stress, ferroptosis, intestinal flora, and other related factors. Furthermore, we intend to discuss potential strategies involving cuproptosis and provide new insights for copper-related vascular aging.
Topics: Copper; Endothelial Cells; Cell Death; Apoptosis; Homeostasis
PubMed: 37976889
DOI: 10.1016/j.biopha.2023.115839 -
Advanced Science (Weinheim,... Jan 2024Cancer immunotherapy has become a mainstream cancer treatment over traditional therapeutic modes. Cancer cells can undergo programmed cell death including ferroptosis,... (Review)
Review
Cancer immunotherapy has become a mainstream cancer treatment over traditional therapeutic modes. Cancer cells can undergo programmed cell death including ferroptosis, pyroptosis, autophagy, necroptosis, apoptosis and cuproptosis which are find to have intrinsic relationships with host antitumor immune response. However, direct use of cell death inducers or regulators may bring about severe side effects that can also be rapidly excreted and degraded with low therapeutic efficacy. Nanomaterials are able to carry them for long circulation time, high tumor accumulation and controlled release to achieve satisfactory therapeutic effect. Nowadays, a large number of studies have focused on nanomedicines-based strategies through modulating cell death modalities to potentiate antitumor immunity. Herein, immune cell types and their function are first summarized, and state-of-the-art research progresses in nanomedicines mediated cell death pathways (e.g., ferroptosis, pyroptosis, autophagy, necroptosis, apoptosis and cuproptosis) with immune response provocation are highlighted. Subsequently, the conclusion and outlook of potential research focus are discussed.
Topics: Nanomedicine; Cell Death; Apoptosis; Pyroptosis; Autophagy
PubMed: 37984863
DOI: 10.1002/advs.202306580 -
Cellular & Molecular Biology Letters Jan 2024TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These proteins are efficient regulators of autophagy, apoptosis, and... (Review)
Review
TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These proteins are efficient regulators of autophagy, apoptosis, and innate immune responses and confer immunity against viruses and bacteria. TRIMs function as receptors or scaffold proteins that target substrates for autophagy-mediated degradation. Most TRIMs interact with the BECN1-ULK1 complex to form TRIMosomes, thereby efficiently targeting substrates to autophagosomes. They regulate the functions of ATG proteins through physical interactions or ubiquitination. TRIMs affect the lipidation of MAP1LC3B1 to form MAP1LC3B2, which is a prerequisite for phagophore and autophagosome formation. In addition, they regulate MTOR kinase and TFEB, thereby regulating the expression of ATG genes. TRIM proteins are efficient regulators of apoptosis and are crucial for regulating cell proliferation and tumor formation. Many TRIM proteins regulate intrinsic and extrinsic apoptosis via the cell surface receptors TGFBR2, TNFRSF1A, and FAS. Mitochondria modulate the anti- and proapoptotic functions of BCL2, BAX, BAK1, and CYCS. These proteins use a multipronged approach to regulate the intrinsic and extrinsic apoptotic pathways, culminating in coordinated activation or inhibition of the initiator and executor CASPs. Furthermore, TRIMs can have a dual effect in determining cell fate and are therefore crucial for cellular homeostasis. In this review, we discuss mechanistic insights into the role of TRIM proteins in regulating autophagy and apoptosis, which can be used to better understand cellular physiology. These findings can be used to develop therapeutic interventions to prevent or treat multiple genetic and infectious diseases.
Topics: Tripartite Motif Proteins; Apoptosis; Apoptosis Regulatory Proteins; Ubiquitination; Autophagy
PubMed: 38225560
DOI: 10.1186/s11658-023-00528-8 -
Trends in Cell Biology Sep 2023Since their discovery, members of the gasdermin (GSDM) family of proteins have been firmly established as executors of pyroptosis, with the N-terminal fragment of most... (Review)
Review
Since their discovery, members of the gasdermin (GSDM) family of proteins have been firmly established as executors of pyroptosis, with the N-terminal fragment of most GSDMs capable of forming pores in the plasma membrane. More recent findings suggest that some GSDMs can drive additional cell death pathways, such as apoptosis and necroptosis, through mechanisms independent of plasma membrane perforation. There is also emerging evidence that by associating with cellular compartments such as mitochondria, peroxisomes, endosomes, and the nucleus, GSDMs regulate cell death-independent aspects of cellular homeostasis. Here, we review the diversity of GSDM function across several cell types and explore how various cellular stresses can promote relocalization - and thus refunctionalization - of GSDMs.
Topics: Humans; Gasdermins; Neoplasm Proteins; Apoptosis; Pyroptosis; Homeostasis; Inflammasomes
PubMed: 37062616
DOI: 10.1016/j.tcb.2023.02.007 -
Parasitology Research Dec 2023Apoptosis is a finely programmed process of cell death in which cells silently dismantle and actively participate in several operations such as immune response,... (Review)
Review
Apoptosis is a finely programmed process of cell death in which cells silently dismantle and actively participate in several operations such as immune response, differentiation, and cell growth. It can be initiated by three main pathways: the extrinsic, the perforin granzyme, and the intrinsic that culminate in the activation of several proteins in charge of tearing down the cell. On the other hand, apoptosis represents an ordeal for pathogens that live inside cells and maintain a strong dependency with them; thus, they have evolved multiple strategies to manipulate host cell apoptosis on their behalf. It has been widely documented that diverse intracellular bacteria, fungi, and parasites can interfere with most steps of the host cell apoptotic machinery to inhibit or induce apoptosis. Indeed, the inhibition of apoptosis is considered a virulence property shared by many intracellular pathogens to ensure productive replication. Some pathogens intervene at an early stage by interfering with the sensing of extracellular signals or transduction pathways. Others sense cellular stress or target the apoptosis regulator proteins of the Bcl-2 family or caspases. In many cases, the exact molecular mechanisms leading to the interference with the host cell apoptotic cascade are still unknown. However, intense research has been conducted to elucidate the strategies employed by intracellular pathogens to modulate host cell death. In this review, we summarize the main routes of activation of apoptosis and present several processes used by different bacteria, fungi, and parasites to modulate the apoptosis of their host cells.
Topics: Animals; Apoptosis; Caspases; Cell Death; Parasites; Fungi
PubMed: 38112844
DOI: 10.1007/s00436-023-08031-x