-
Biochimica Et Biophysica Acta Dec 2013Apoptosis and necrosis are the two major modes of cell death, the molecular mechanisms of which have been extensively studied. Although initially thought to constitute... (Review)
Review
Apoptosis and necrosis are the two major modes of cell death, the molecular mechanisms of which have been extensively studied. Although initially thought to constitute mutually exclusive cellular states, recent findings reveal cellular contexts that require a balanced interplay between these two modes of cellular demise. Several death initiator and effector molecules, signaling pathways and subcellular sites have been identified as key mediators in both processes, either by constituting common modules or alternatively by functioning as a switch allowing cells to decide which route to take, depending on the specific situation. Importantly, autophagy, which is a predominantly cytoprotective process, has been linked to both types of cell death, serving either a pro-survival or pro-death function. Here we review the recent literature that highlights the intricate interplay between apoptosis, necrosis and autophagy, focusing on the relevance and impact of this crosstalk in normal development and in pathology. This article is part of a Special Section entitled: Cell Death Pathways.
Topics: Apoptosis; Autophagy; Humans; Models, Biological; Necrosis; Signal Transduction
PubMed: 23770045
DOI: 10.1016/j.bbamcr.2013.06.001 -
Nature Reviews. Nephrology May 2023Disorders of cell number that result from an imbalance between the death of parenchymal cells and the proliferation or recruitment of maladaptive cells contributes to... (Review)
Review
Disorders of cell number that result from an imbalance between the death of parenchymal cells and the proliferation or recruitment of maladaptive cells contributes to the pathogenesis of kidney disease. Acute kidney injury can result from an acute loss of kidney epithelial cells. In chronic kidney disease, loss of kidney epithelial cells leads to glomerulosclerosis and tubular atrophy, whereas interstitial inflammation and fibrosis result from an excess of leukocytes and myofibroblasts. Other conditions, such as acquired cystic disease and kidney cancer, are characterized by excess numbers of cyst wall and malignant cells, respectively. Cell death modalities act to clear unwanted cells, but disproportionate responses can contribute to the detrimental loss of kidney cells. Indeed, pathways of regulated cell death - including apoptosis and necrosis - have emerged as central events in the pathogenesis of various kidney diseases that may be amenable to therapeutic intervention. Modes of regulated necrosis, such as ferroptosis, necroptosis and pyroptosis may cause kidney injury directly or through the recruitment of immune cells and stimulation of inflammatory responses. Importantly, multiple layers of interconnections exist between different modalities of regulated cell death, including shared triggers, molecular components and protective mechanisms.
Topics: Humans; Apoptosis; Kidney; Necrosis; Acute Kidney Injury; Ferroptosis
PubMed: 36959481
DOI: 10.1038/s41581-023-00694-0 -
Molecules (Basel, Switzerland) Dec 2022Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of... (Review)
Review
Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. Recently, ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. Recent studies have also reported that ZBP1 induces necroptosis in non-viral infections and mediates necrotic signal transduction by a unique mechanism. This review highlights the discovery of ZBP1 and its novel findings in necroptosis and provides an insight into its critical role in the crosstalk between different types of cell death, which may represent a new therapeutic option.
Topics: Humans; Necroptosis; Necrosis; Virus Diseases
PubMed: 36615244
DOI: 10.3390/molecules28010052 -
The American Journal of Pathology Jan 1995The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis,... (Review)
Review
The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage.
Topics: Animals; Apoptosis; Cell Death; Humans; Necrosis
PubMed: 7856735
DOI: No ID Found -
Journal of Natural Products Jul 2022Oxidative stress plays an important role in acetaminophen (APAP)-induced hepatotoxicity. Platanosides (PTSs) isolated from the American sycamore tree () represent a... (Review)
Review
Oxidative stress plays an important role in acetaminophen (APAP)-induced hepatotoxicity. Platanosides (PTSs) isolated from the American sycamore tree () represent a potential new four-molecule botanical drug class of antibiotics active against drug-resistant infectious disease. Preliminary studies have suggested that PTSs are safe and well tolerated and have antioxidant properties. The potential utility of PTSs in decreasing APAP hepatotoxicity in mice in addition to an assessment of their potential with APAP for the control of infectious diseases along with pain and pyrexia associated with a bacterial infection was investigated. On PTS treatment in mice, serum alanine aminotransferase (ALT) release, hepatic centrilobular necrosis, and 4-hydroxynonenal (4-HNE) were markedly decreased. In addition, inducible nitric oxide synthase (iNOS) expression and c-Jun--terminal kinase (JNK) activation decreased when mice overdosed with APAP were treated with PTSs. Computational studies suggested that PTSs may act as JNK-1/2 and Keap1-Nrf2 inhibitors and that the isomeric mixture could provide greater efficacy than the individual molecules. Overall, PTSs represent promising botanical drugs for hepatoprotection and drug-resistant bacterial infections and are effective in protecting against APAP-related hepatotoxicity, which decreases liver necrosis and inflammation, iNOS expression, and oxidative and nitrative stresses, possibly by preventing persistent JNK activation.
Topics: Acetaminophen; Animals; Chemical and Drug Induced Liver Injury; Drug Combinations; Glycosides; Kelch-Like ECH-Associated Protein 1; Liver; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Necrosis; Oxidative Stress; Phenols
PubMed: 35815804
DOI: 10.1021/acs.jnatprod.2c00324 -
Cell Proliferation Mar 2021Spinal cord injury (SCI) always leads to functional deterioration due to a series of processes including cell death. In recent years, programmed cell death (PCD) is... (Review)
Review
Spinal cord injury (SCI) always leads to functional deterioration due to a series of processes including cell death. In recent years, programmed cell death (PCD) is considered to be a critical process after SCI, and various forms of PCD were discovered in recent years, including apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis and paraptosis. Unlike necrosis, PCD is known as an active cell death mediated by a cascade of gene expression events, and it is crucial for elimination unnecessary and damaged cells, as well as a defence mechanism. Therefore, it would be meaningful to characterize the roles of PCD to not only enhance our understanding of the pathophysiological processes, but also improve functional recovery after SCI. This review will summarize and explore the most recent advances on how apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis and paraptosis are involved in SCI. This review can help us to understand the various functions of PCD in the pathological processes of SCI, and contribute to our novel understanding of SCI of unknown aetiology in the near future.
Topics: Animals; Apoptosis; Autophagy; Cell Death; Humans; Necroptosis; Necrosis; Spinal Cord Injuries
PubMed: 33506613
DOI: 10.1111/cpr.12992 -
Biomedicine & Pharmacotherapy =... Dec 2023Diabetes mellitus is a metabolic disease caused by disorders of insulin secretion and utilization. Long-term hyperglycemia, insulin resistance, and disorders of glucose... (Review)
Review
Diabetes mellitus is a metabolic disease caused by disorders of insulin secretion and utilization. Long-term hyperglycemia, insulin resistance, and disorders of glucose and lipid metabolism cause vascular endothelial cell damage. Endothelial dysfunction is a key feature of diabetic vascular complications such as diabetic nephropathy, retinopathy, neuropathy, and atherosclerosis. Importantly, cell death is thought to be a key factor contributing to vascular endothelial injury. Morphologically, cell death can be divided into three forms: type I apoptosis, type II autophagy, and type III necrosis. According to the difference in function, cell death can be divided into accidental cell death (ACD) and regulated cell death (RCD). RCD is a controlled process involving numerous proteins and precise signaling cascades. Multiple subroutines covered by RCD may be involved in diabetic endothelial dysfunction, including apoptosis, autophagy, necroptosis, pyroptosis, entosis, ferroptosis, ferroautophagy, parthanatos, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, cuproptosis, and PANoptosis. This article briefly reviews the mechanism and significance of cell death associated with diabetic endothelial dysfunction, which will help deepen the understanding of diabetic endothelial cell death and provide new therapeutic ideas.
Topics: Humans; Cell Death; Diabetes Mellitus; Apoptosis; Necrosis; Regulated Cell Death
PubMed: 37918258
DOI: 10.1016/j.biopha.2023.115802 -
The Journal of Bone and Joint Surgery.... Jun 2020➢. Clinicians should exercise a high level of suspicion in at-risk patients (those who use corticosteroids, consume excessive alcohol, have sickle cell disease, etc.)... (Review)
Review
➢. Clinicians should exercise a high level of suspicion in at-risk patients (those who use corticosteroids, consume excessive alcohol, have sickle cell disease, etc.) in order to diagnose osteonecrosis of the femoral head in its earliest stage. ➢. Nonoperative treatment modalities have generally been ineffective at halting progression. Thus, nonoperative treatment is not appropriate in early stages when one is attempting to preserve the native joint, except potentially on rare occasions for small-sized, medially located lesions, which may heal without surgery. ➢. Joint-preserving procedures should be attempted in early-stage lesions to save the femoral head. ➢. Cell-based augmentation of joint-preserving procedures continues to show promising results, and thus should be considered as an ancillary treatment method that may improve clinical outcomes. ➢. The outcomes of total hip arthroplasty in the setting of osteonecrosis are excellent, with results similar to those in patients who have an underlying diagnosis of osteoarthritis.
Topics: Arthroplasty, Replacement, Hip; Bone Transplantation; Decompression, Surgical; Femur Head Necrosis; Humans
PubMed: 32282421
DOI: 10.2106/JBJS.19.01271 -
Journal of Clinical Oncology : Official... May 2023Immune checkpoint inhibitors combined with antiangiogenic therapy reportedly have potential synergistic antitumor activity. We investigated the activity and safety of...
PURPOSE
Immune checkpoint inhibitors combined with antiangiogenic therapy reportedly have potential synergistic antitumor activity. We investigated the activity and safety of this regimen for recurrent/metastatic nasopharyngeal carcinoma (NPC).
METHODS
This single-arm, Simon two-stage study enrolled patients with recurrent/metastatic NPC who were refractory to at least first-line systemic therapy and treatment-naive to immune checkpoint inhibitors. The patients received camrelizumab 200 mg once every 3 weeks and apatinib 250 mg once per day. The primary end point was the objective response rate. Key secondary end points included disease control rate, progression-free survival, duration of response, overall survival, and safety.
RESULTS
Between October 14, 2020, and December 23, 2021, 58 patients were enrolled, and all were included in the efficacy and safety analysis set. The objective response rate was 65.5% (95% CI, 51.9 to 77.5), and the disease control rate was 86.2% (95% CI, 74.6 to 93.9). The median duration of response was not reached, and the median progression-free survival was 10.4 months (95% CI, 7.2 to 13.6), with a median follow-up duration of 12.4 months (range, 2.1-19.9 months). Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 34 (58.6%) patients, with the most common being hypertension (19.0%), nasopharyngeal necrosis (15.5%), headache (12.1%), AST elevation (10.3%), and creatine phosphokinase elevation (10.3%). Sixteen (27.6%) patients discontinued apatinib treatment before progression because of unbearable TRAEs, and the most common complication was nasopharyngeal necrosis (9/16; 56.3%). Recurrent nasopharyngeal lesions (odds ratio, 5.94 [95% CI, 1.45 to 24.24]) and reirradiation (odds ratio, 5.33 [95% CI, 1.15 to 24.79]) were significantly positively correlated with nasopharyngeal necrosis.
CONCLUSION
Camrelizumab plus apatinib had promising antitumor activity in patients with refractory recurrent/metastatic NPC who failed first-line therapy. Moderate to severe TRAEs were experienced by 58.6%, including nasopharyngeal necrosis associated with local recurrence and a history of reirradiation.
Topics: Humans; Nasopharyngeal Carcinoma; Immune Checkpoint Inhibitors; Neoplasm Recurrence, Local; Nasopharyngeal Neoplasms; Necrosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36735896
DOI: 10.1200/JCO.22.01450 -
The Journal of Clinical Investigation Aug 2023The liver can fully regenerate after partial resection, and its underlying mechanisms have been extensively studied. The liver can also rapidly regenerate after injury,...
The liver can fully regenerate after partial resection, and its underlying mechanisms have been extensively studied. The liver can also rapidly regenerate after injury, with most studies focusing on hepatocyte proliferation; however, how hepatic necrotic lesions during acute or chronic liver diseases are eliminated and repaired remains obscure. Here, we demonstrate that monocyte-derived macrophages (MoMFs) were rapidly recruited to and encapsulated necrotic areas during immune-mediated liver injury and that this feature was essential in repairing necrotic lesions. At the early stage of injury, infiltrating MoMFs activated the Jagged1/notch homolog protein 2 (JAG1/NOTCH2) axis to induce cell death-resistant SRY-box transcription factor 9+ (SOX9+) hepatocytes near the necrotic lesions, which acted as a barrier from further injury. Subsequently, necrotic environment (hypoxia and dead cells) induced a cluster of complement 1q-positive (C1q+) MoMFs that promoted necrotic removal and liver repair, while Pdgfb+ MoMFs activated hepatic stellate cells (HSCs) to express α-smooth muscle actin and induce a strong contraction signal (YAP, pMLC) to squeeze and finally eliminate the necrotic lesions. In conclusion, MoMFs play a key role in repairing the necrotic lesions, not only by removing necrotic tissues, but also by inducing cell death-resistant hepatocytes to form a perinecrotic capsule and by activating α-smooth muscle actin-expressing HSCs to facilitate necrotic lesion resolution.
Topics: Humans; Actins; Liver; Hepatocytes; Macrophages; Hepatic Stellate Cells; Necrosis; Liver Neoplasms
PubMed: 37338984
DOI: 10.1172/JCI166954