Necroptosis: A new way of dying?

Hanson, Britt

doi:10.1080/15384047.2016.1210732

Cited by 73 publications

(67 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it was recently shown that activation of PARP1 in the presence of high levels of DNA damage directly suppresses glycolysis via inhibition of hexokinase 1, leading to cell death [55]. Another form of cell death termed necroptosis is also activated in cells harboring DNA damage (for a review see [56]). Cellular debris emanating from dead or dying cells is normally cleared by phagocytes and macrophages (for a review see [57].…”

Section: Mechanisms Associated With Defective Dna Repair and Slementioning

confidence: 99%

DNA repair and systemic lupus erythematosus

2017

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with no known cure that affects at least five million people worldwide. Monozygotic twin concordance and familial aggregation studies strongly suggest that lupus results from genetic predisposition along with environmental exposures including UV light. The majority of the common risk alleles associated with genetic predisposition to SLE map to genes associated with the immune system. However, evidence is emerging that implicates a role for aberrant DNA repair in the development of lupus. Here we summarize our current knowledge of the potential association of lupus with mutations in DNA repair genes. We also discuss how defective or aberrant DNA repair could lead to the development of lupus.

show abstract

Section: Mechanisms Associated With Defective Dna Repair and Slementioning

confidence: 99%

DNA repair and systemic lupus erythematosus

2017

View full text Add to dashboard Cite

show abstract

“…However, apoptosis is a programmed cell death modality, generally triggered by physiological processes, whereas necrosis is an uncontrolled and accidental cell death modality triggered by pathological processes. Necroptosis, a novel cell death modality, involves the loss of membrane integrity and occurs by a programmable mechanism with a characteristic necrotic cell death phenotype [10-13]. Necroptosis is initiated by the activation of receptor interacting protein (RIP) kinases and mixed-lineage kinase domain-like protein (MLKL).…”

Section: Introductionmentioning

confidence: 99%

Necroptosis Contributes to Urban Particulate Matter-Induced Airway Epithelial Injury

Luo

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Necroptosis, a form of programmed necrosis, is involved in the pathologic process of several kinds of pulmonary diseases. However, the role of necroptosis in particulate matter (PM)–induced pulmonary injury remains unclear. The objective of this study is to investigate the involvement of necroptosis in the pathogenesis of PM-induced toxic effects in pulmonary inflammation and mucus hyperproduction, both in vitro and in vivo. Methods: PM was administered into human bronchial epithelial (HBE) cells or mouse airways, and the inflammatory response and mucus production were assessed. The mRNA expressions of IL6, IL8 and MUC5AC in HBE cells and Cxcl1, Cxcl2, and Gm-csf in the lung tissues were detected by quantitative real-time RT-PCR. The secreted protein levels of IL6 and IL8 in culture supernatants and Cxcl1, Cxcl2, and Gm-csf in bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA). We used Western blot to measure the protein expressions of necroptosis-related proteins (RIPK1, RIPK3, and Phospho-MLKL), NF-κB (P65 and PP65), AP-1 (P-c-Jun and P-c-Fos) and MUC5AC. Cell necrosis and mitochondrial ROS were detected using flow cytometry. In addition, pathological changes and scoring of lung tissue samples were monitored using hemoxylin and eosin (H&E), periodic acid-schiff (PAS) and immunohistochemistry staining. Results: Our study showed that PM exposure induced RIP and MLKL-dependent necroptosis in HBE cells and in mouse lungs. Managing the necroptosis inhibitor Necrostatin-1 (Nec-1) and GSK’872, specific molecule inhibitors of necroptosis, markedly reduced PM-induced inflammatory cytokines, e.g., IL6 and IL8, and MUC5AC in HBE cells. Similarly, administering Nec-1 significantly reduced airway inflammation and mucus hyperproduction in PM-exposed mice. Mechanistically, we found PM–induced necroptosis was mediated by mitochondrial reactive oxygen species-dependent early growth response gene 1, which ultimately promoted inflammation and mucin expression through nuclear factor κB and activator protein-1 pathways, respectively. Conclusions: Our results demonstrate that necroptosis is involved in the pathogenesis of PM–induced pulmonary inflammation and mucus hyperproduction, and suggests that it may be a novel target for treatment of airway disorders or disease exacerbations with airborne particulate pollution.

show abstract

“…In contrast to the relatively "clean" death associated with apoptosis, cells that are necroptotic release their intracellular contents en masse into the surrounding milieu, due to the plasma membrane rupture mediated by MLKL. The highly inflammatory response that occurs following intracellular content release into the microenvironment (necroinflammation) after necroptosis may be a consequence of several of these intracellular components, since the cytosol can contain various pro-inflammatory cytokines (induced by NF-κB and p38), as well as constitutive damageassociated molecular patterns (DAMPs) [45][46][47].…”

Section: Apoptosis Vs Necroptosismentioning

confidence: 99%

“…Pro-inflammatory cytokines and chemokines are released from necroptotic corpses. Cytokines such as TNF can lead to further activation of cell death pathways including necroptosis in surrounding cells [46,47]. Moreover, these pro-inflammatory mediators can directly influence cells of the immune system such as macrophages, leading to further inflammatory output in what could be described as a positive feedback loop for inflammation.…”

Section: Damping Out Immune Silencementioning

confidence: 99%

Crashing the computer: apoptosis vs. necroptosis in neuroinflammation

2018

View full text Add to dashboard Cite

Programmed cell death (PCD) plays critical roles in development, homeostasis, and both control and progression of a plethora of diseases, including cancer and neurodegenerative pathologies. Besides classical apoptosis, several different forms of PCD have now been recognized, including necroptosis. The way a cell dies determines the reaction of the surrounding environment, and immune activation in response to cell death proceeds in a manner dependent on which death pathways are activated. Apoptosis and necroptosis are major mechanisms of cell death that typically result in opposing immune responses. Apoptotic death usually leads to immunologically silent responses whereas necroptotic death releases molecules that promote inflammation, a process referred to as necroinflammation. Diseases of the nervous system, in particular neurodegenerative diseases, are characterized by neuronal death and progressive neuroinflammation. The mechanisms of neuronal death are not well defined and significant cross-talk between pathways has been suggested. Moreover, it has been proposed that the dying of neurons is a catalyst for activating immune cells in the brain and sustaining inflammatory output. In the current review we discuss the effects of apoptotis and necroptosis on inflammatory immune activation, and evaluate the roles of each cell death pathway in a variety of pathologies with specific focus on neurodegeneration. A putative model is proposed for the regulation of neuronal death and neuroinflammation that features a role for both the apoptotic and necroptotic pathways in disease establishment and progression.

show abstract

Necroptosis: A new way of dying?

Cited by 73 publications

References 120 publications

DNA repair and systemic lupus erythematosus

DNA repair and systemic lupus erythematosus

Necroptosis Contributes to Urban Particulate Matter-Induced Airway Epithelial Injury

Crashing the computer: apoptosis vs. necroptosis in neuroinflammation

Contact Info

Product

Resources

About