• Many of the pro-inflammatory pathways activated during cell death occur upon mitochondrial outer membrane permeabilization (MOMP), the pivotal commitment point to cell death during mitochondrial apoptosis. (nature.com)
  • Caspases, while dispensable for cell death during mitochondrial apoptosis, inhibit activation of pro-inflammatory pathways after MOMP. (nature.com)
  • Some of these mitochondrial-activated inflammatory pathways can be traced back to the bacterial ancestry of mitochondria. (nature.com)
  • The bacterial origin of mitochondria suggests that inflammatory pathways found in cytosol-invading bacteria may be relevant to mitochondrial-driven inflammation after MOMP. (nature.com)
  • Titanium dioxide (TiO2) nanoparticle s induce JB6 cell apoptosis through activation of the caspase-8/Bid and mitochondrial pathways. (cdc.gov)
  • In particular, we will discuss the modifications in intrinsic and extrinsic apoptotic pathways caused by proteins encoded by HPV early genes. (mdpi.com)
  • Markers of Parkinson (PD) and Alzheimer (AD) diseases are able to induce innate immune pathways induced by alterations in mitochondrial Ca 2+ homeostasis leading to neuroinflammation. (frontiersin.org)
  • Disturbances in mitochondrial dynamics may influence many cellular and molecular pathways, as calcium-dependent immune activation, transcription factors phosphorylation, cytokine secretion, organelle transference and even cell death. (frontiersin.org)
  • Chang CY, Shen CY, Kang CK, Sher YP, Sheu WH, Chang CC, Lee TH (2014) Tau protects HK-2 cells from oxidized LDL-induced cytotoxicity via the ROS-mediated mitochondrial and p53-related apoptotic pathways. (springer.com)
  • Furthermore, immunoblotting studies revealed the activation of intrinsic and maybe extrinsic apoptosis pathways by OEO/thymol. (irost.org)
  • There is increasing evidence that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. (spandidos-publications.com)
  • The caspases can be activated through either the intrinsic (mitochondrial mediated) or extrinsic (death receptor mediated) apoptotic pathways. (geneontology.org)
  • induced apoptosis by activating death receptor and mitochondria dependent apoptotic signaling pathways in COLO 205 cells. (1library.net)
  • Overexpression of HSP70 can provide a selective survival advantage to tumor cells in part due to its ability to inhibit multiple pathways of cell death, including both intrinsic and extrinsic apoptosis. (biomedcentral.com)
  • Kadeyala PK, Sannadi S, Gottipolu RR (2013) Alterations in apoptotic caspases and antioxidant enzymes in arsenic exposed rat brain regions: reversal effect of essential metals and a chelating agent. (springer.com)
  • Selected cell lines that displayed sensitivity towards the specific BH3 mimetics underwent intrinsic apoptosis, which was characterized by loss of mitochondrial membrane potential, exposure of phosphatidylserine and activation of caspases. (uni-frankfurt.de)
  • mitochondrial membrane permeability → cytochrome c & AIF → activates caspases → death. (howmed.net)
  • Breaching the mitochondrial OM releases apoptogenic factors, including cytochrome c and DIABLO (also known as Smac), which activate a group of aspartate-specific proteases known as caspases ( Youle and Strasser, 2008 ). (biologists.com)
  • By contrast, the extrinsic apoptotic pathway can activate caspases without the participation of mitochondria. (biologists.com)
  • Once activated by their respective upstream signals, caspase-8 and -9 may cleave and activate downstream executioner caspases -3 and -7, which, in turn, cleave a plethora of target proteins, resulting in apoptotic death ( 6 - 8 ). (spandidos-publications.com)
  • BCL2 proteins are described as 'crucial regulators of apoptosis' (PMID:15868100)and the intrinsic apoptosis pathway is initiated by the release of mitochondrial cytochrome c into the cytoplasm, which results in the activation of caspases (15102863) - help in generating a defintion for intrinsic apoptosis? (geneontology.org)
  • Diclofenac inhibited ER-stress-induced apoptosis of SH-SY5Y cells by suppressing the activation of caspases in the intrinsic apoptotic pathway. (elsevierpure.com)
  • Radiation and other agents induce caspase activation fundamentally via the mitochondrial pathway, which includes mitochondrial integration of apoptotic signals and the subsequent release of cytochrome c into the cytosol ( 5 , 9 , 10 ). (spandidos-publications.com)
  • The intrinsic apoptotic pathway is characterized by permeabilisation of the mitochondria and release of cytochrome c into the cytoplasm. (geneontology.org)
  • Increased release of cytochrome c upon rhSP-D confirmed the activation of mitochondrial intrinsic apoptotic pathway in both the cell types. (canadianjbiotech.com)
  • MG132-mediated aggresome formation upregulated ER stress sensors, the mitochondrial membrane potential drop, cytochrome c release to the cytoplasm, and activation of caspase-9 and -3. (cardiff.ac.uk)
  • Apoptotic markers of cytochrome c (Cyt c ), Bax, and Bcl-2 were evaluated by RT-PCR. (biomedcentral.com)
  • The central event in the 'intrinsic' pathway is the mitochondrial outer membrane permeabilization (MOMP), which leads to the release of cytochrome c. (kegg.jp)
  • Permeabilised mitochondria trigger inflammation, in part, through the release of mitochondrial-derived damage-associated molecular patterns (DAMPs). (nature.com)
  • Mitochondria contain several DAMPs that can be released upon mitochondrial stress or damage (Fig. 1 ). (nature.com)
  • Within the cell, TSPO is predominantly located in mitochondria, specifically in the outer mitochondrial membrane. (uni-regensburg.de)
  • Further studies demonstrated that TiO2 nanoparticle s induced significant changes in mitochondrial membrane permeability, suggesting the involvement of mitochondria in the apoptotic process. (cdc.gov)
  • Additionally, exacerbated type I IFN responses triggered by mitochondrial DNA (mtDNA), failures in mitophagy, ER-mitochondria communication and mtROS production promote neurodegeneration. (frontiersin.org)
  • 4) Conclusions: PL treatment could potentially protect the urothelium from apoptosis during ischemia/hypoxia by a mechanism that modulates the expression of HIF1α, the mitochondria-mediated intrinsic apoptotic pathway, and reduces ROS. (beaumont.org)
  • and the intrinsic pathway, which is activated by cellular stress and is regulated primarily at the level of mitochondria by the Bcl-2 family of proteins ( Fig. 1 ). (biologists.com)
  • The extrinsic pathway is associated with membrane receptors and their ligands, and the intrinsic pathway is dependent on mitochondria ( 5 ). (spandidos-publications.com)
  • [ 2 ] , is caused by a failure of apoptotic mechanisms to maintain lymphocyte homeostasis leading to abnormal lymphocyte survival. (medscape.com)
  • ALPS, as this disorder was subsequently named, has been shown to represent a failure of apoptotic mechanisms. (medscape.com)
  • Taken at face value, senile cataract is intimately associated with the increased risk of oxidative stress, which levies irrevocable changes in the lenticular proteins that impel the lens epithelial cells to the apoptotic phase. (molvis.org)
  • BH3 mimetics are novel anticancer therapeutics that induce apoptosis by targeting anti‐apoptotic BCL‐2 proteins. (uni-frankfurt.de)
  • Highly specific inhibitors of the main anti-apoptotic proteins BCL-2, BCL‐XL and MCL‐1 promise new opportunities for the treatment of AML. (uni-frankfurt.de)
  • However, it is currently unclear which of these anti-apoptotic BCL-2 proteins represents the most promising target in AML. (uni-frankfurt.de)
  • Label-free quantitative proteomic analyses using liquid chromatography in conjunction with a tandem mass spectrometry (LC-MS/MS) system showed significant alteration of mitochondrial, cytosolic, nuclear and cytoskeletal proteins in fetal brains exposed prenatally to alcohol [ 17 ]. (biomedcentral.com)
  • The intrinsic apoptotic pathway is initiated in response to a variety of stress signals ( Willis and Adams, 2005 ), and a complex interplay of Bcl-2 proteins relays this signal to the mitochondrial outer membrane (OM) to initiate Bak and Bax activation, oligomerisation and OM damage ( Fig. 1 ). (biologists.com)
  • Anti-apoptotic strategies include inhibition of caspase, poly [ADP-ribose] polymerase (PARP), and Bcl-2 proteins as well as induction of the PKB/Akt pathway and inhibitors of apoptosis (IAP) family of proteins. (biomedcentral.com)
  • PMID:14996496, table 1 provides links to papers that describe subcellular location of many pro- and anti-apoptotic proteins. (geneontology.org)
  • At least some of these proteins are likely to be found within the MICOS complex (mitochondrial contact site and cristae organizing system). (db-engine.de)
  • It largely regulated at the mitochondrial outer membrane (MOM) by the pro- and anti-apoptotic members of the B cell lymphoma 2 (Bcl-2) family of proteins. (cancer-research-network.com)
  • MOMP results from an ordered series of steps beginning with the activation of one or more Bcl-2 homology 3 proteins (BH3-proteins) or releasing previously activated pro-apoptotic proteins Bax or Bak from inhibition by an anti-apoptotic protein of the Bcl-2 family. (cancer-research-network.com)
  • Furthermore, HIF-1 actively limits the mitochondrial consumption of pyruvate at two levels: (i) through the enzyme PDK (PDH-kinase), which in turn inhibits PDH activity preventing the conversion of pyruvate into acetyl CoA, and thereby limiting mitochondrial metabolism of pyruvate [ 6 ] and (ii) through the direct activation of LDH [ 7 , 8 ]. (hindawi.com)
  • Indeed, OEO/thymol increased the Reactive Oxygen Species (ROS) level leading to mitochondrial membrane potential (MMP, ΔΨm) loss, caspase-3 activation and DNA damage caused S-phase cell cycle arrest. (irost.org)
  • All three triggered mitochondrial damage, caspase activation, and cell death. (medhelp.org)
  • However, in certain cell types, the extrinsic pathway also induces mitochondrial damage by cleaving the pro-apoptotic Bcl-2 family protein Bid to its activated truncated form (tBid), which leads to Bak and Bax activation. (biologists.com)
  • Radiation induces caspase activation fundamentally via the mitochondrial pathway. (spandidos-publications.com)
  • The central element in the mitochondrial pathway is a specialised protein complex, the apoptosome, which enables and facilitates the activation of procaspase 9. (spandidos-publications.com)
  • Mechanistically, we witnessed an important reduction in the expression levels of Mcl 1, a member of the Bcl 2 family, in line with activation of the intrinsic apoptotic machinery. (igfprotein.com)
  • Knockdown of CHOP attenuated the ER stress-induced cleavage of caspase-9, which is caused by intrinsic pathway activation. (cardiff.ac.uk)
  • HSP70 reduces caspase activation (mainly caspase-3) and suppresses mitochondrial damage and nuclear fragmentation. (biomedcentral.com)
  • In conclusion, evidence indicated that TiO2 nanoparticle s exhibit higher cytotoxicity and apoptotic induction compared to fine particles in JB6 cells. (cdc.gov)
  • Astrakurkurol cytotoxicity was based on caspase-8-mediated intrinsic apoptotic pathway and was associated with inhibition at Akt and NF-κB pathway. (reading.ac.uk)
  • Mitochondrial outer membrane permeabilisation (MOMP) is the point of no return in many forms of apoptotic cell death. (biologists.com)
  • The current development of anti-cancer agents that target the Bcl-2 protein family is showing considerable promise, although how this targeting triggers Bak and Bax to perform their crucial function of mitochondrial outer membrane permeabilisation (MOMP) is not clear. (biologists.com)
  • MSN-125 prevents mitochondrial outer membrane permeabilization. (cancer-research-network.com)
  • How do C-type lectins tailor adaptive immunity following phagocytosis of apoptotic cells? (nature.com)
  • Phagocytosis of apoptotic bodies. (howmed.net)
  • Various assays were used to investigate the stimulatory effects of the purified rFg14-3-3e protein on specific functions of goat PBMCs, including cytokine secretion, proliferation, migration, nitric oxide (NO) production, phagocytosis, and apoptotic capabilities. (biomedcentral.com)
  • Two decades later, pioneering studies suggested that lectin-like molecules constitutively expressed on the surface of macrophages can selectively recognize changes on glycans decorating the surface of apoptotic thymocytes, 4 , 5 although these studies likewise did not provide substantial insight into the mechanisms by which lectin-glycan interactions regulate cell death. (nature.com)
  • To avoid elimination by this mechanism, human papillomaviruses (HPV) have developed several mechanisms that enable the cells they infect to elude both extrinsic and intrinsic apoptosis. (mdpi.com)
  • Collectively, our findings reveal an integral role of SP-D in immune surveillance against prostate cancer mediated by two distinct mitochondrial apoptotic mechanisms. (canadianjbiotech.com)
  • This review discusses the recent findings regarding sarcopenia, the intrinsic, and extrinsic mechanisms involved in the onset and progression of this disease and the treatment approaches that have been developed based on testosterone deficiency and their implications. (frontiersin.org)
  • Environmental factors that can detect specific IgE antibodies against most low-molecular- affect the initiation of occupational asthma include the intrinsic weight agents has resulted in a search for alternative or characteristics of causative agents as well as the influence of the complementary physiopathologic mechanisms leading to airway level and route of exposure at the workplace. (cdc.gov)
  • On the other hand, regulation of mitochondrial dynamics is essential for CNS health maintenance and leading to the induction of IL-10 and reduction of TNF-α secretion, increased cell viability and diminished cell injury in addition to reduced oxidative stress. (frontiersin.org)
  • Platelet Lysate Therapy Attenuates Hypoxia Induced Apoptosis in Human Uroepithelial SV-HUC-1 Cells through Regulating the Oxidative Stress and Mitochondrial-Mediated Intrinsic Apoptotic Pathway. (beaumont.org)
  • Extracellular signals activating death receptors triggers the extrinsic pathway, and intracellular stress activates the intrinsic pathway. (cancer-research-network.com)
  • TNF family of ligands activates anti-apoptotic or cell-survival signals as well as apoptotic signals. (kegg.jp)
  • In the intrinsic pathway the cell kills itself because it senses cell stress, while in the extrinsic pathway the cell kills itself because of signals from other cells. (wikipedia.org)
  • However, the ability of HPV-infected cells to resist apoptotic signals renders such therapies ineffective. (mdpi.com)
  • They play a substantial role in survival and cell death, since pro-apoptotic signals can propagate through them. (biomedcentral.com)
  • It is the balance between the pro-apoptotic and anti-apoptotic signals that eventually determines whether cells will undergo apoptosis, survive or proliferate. (kegg.jp)
  • TSPO is a ubiquitous mitochondrial protein and is involved in numerous biological functions. (uni-regensburg.de)
  • We recently reported that a key step leading to Bak homo-oligomerisation following an apoptotic stimulus involves transient exposure of the Bak BH3 domain before it binds to the hydrophobic groove of another activated Bak molecule to form a novel symmetric dimer. (biologists.com)
  • Nonetheless their association with mitochondrial dysfunction highlights this organelle as an important player during CNS homeostasis and disease. (frontiersin.org)
  • These DAMPs include mitochondrial DNA (mtDNA), cardiolipin, N-formyl peptides (NFPs), and reactive oxygen species (ROS) but also metabolites such as adenosine triphosphate (ATP) and succinate [ 3 ]. (nature.com)
  • Due to its bacterial ancestry, mitochondrial formylation of methionine is required for translation initiation of mtDNA-derived mRNA [ 7 ] and will therefore be recognised by the same formyl peptide receptors. (nature.com)
  • Thus, understanding the mechanism of apoptosis gives detailed insights of anti-apoptotic molecular targets. (biomedcentral.com)
  • In addition, as the intrinsic apoptotic pathway seems to have evolved at the same time as multicellular organisms, whereas the extrinsic pathway is a more recent evolutionary development in veterbrates, it is felt the intrinsic mechanism was more suited to a multi-organism curation project. (geneontology.org)
  • ALPS is rarely caused by a defect of mitochondrial apoptosis or intrinsic pathway. (medscape.com)
  • An NRAS mutation has been identified that represents the first identified case of ALPS resulting from a defect in the intrinsic, or mitochondrial, apoptotic pathway. (medscape.com)
  • Moreover, tBid mediated ROS generation, which triggered mitochondrial dysfunction and activated the mitochondrial apoptotic events. (reading.ac.uk)
  • it both initiates a proteolytic cascade of pro-apoptotic enzymes and damages mitochondrial function. (biologists.com)
  • Total RNA was isolated on P16, and the relative abundance of mRNA of the crystallin structural genes, redox components, and apoptotic cascade were ascertained with real-time PCR with reference to the internal control β-actin . (molvis.org)
  • Real-time PCR analysis showed the crystallin genes ( αA- , βB1- , γD- ) and redox cycle components ( Cat , SOD-1 , Gpx ) were downregulated, the apoptotic components were upregulated, and antiapoptotic Bcl-2 was downregulated in Group II. (molvis.org)
  • C-PC treatment possibly prevented cataractogenesis triggered by sodium selenite, by regulating the lens crystallin, redox genes, and apoptotic cascade mRNA expression and thus maintains lens transparency. (molvis.org)
  • Unlike necrosis, apoptosis produces cell fragments called apoptotic bodies that phagocytes are able to engulf and remove before the contents of the cell can spill out onto surrounding cells and cause damage to them. (wikipedia.org)
  • These findings suggest that inter- the apoptotic destruction of lymphocytes and dendritic ventions aimed at reducing the extent of immune cell apop- tosis could improve outcomes for a variety of severe cells could have a particularly adverse effect on disease human infections, including those caused by emerging outcome. (cdc.gov)
  • In contrast to normal cells, most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactate fermentation, even in the presence of oxygen, a less efficient metabolism compared to a low rate of glycolysis followed by mitochondrial oxidation of pyruvate [ 2 ]. (hindawi.com)
  • The detection of apoptotic cells and CM-H2DCFDA, an indicator of reactive oxygen species (ROS) in cells, was analyzed by flow cytometry. (beaumont.org)
  • Thapsigargin and tunicamycin each significantly activated caspase-3, -9, and -2 in the intrinsic apoptotic pathway in SH-SY5Y cells. (elsevierpure.com)
  • Thapsigargin and tunicamycin decreased the mitochondrial membrane potential in SH-SY5Y cells. (elsevierpure.com)
  • In recent studies, YC-1 has been investigated for its apoptotic effects against cancer cells [7-9]. (1library.net)
  • Co-Treatment with ginseng also reduced the expression of apoptotic markers and increased the proliferative indexes in granulosa and theca cells in pre-antral and antral follicles and also in stroma cells, in comparison to the nicotine group ( P = 0.001). (biomedcentral.com)
  • This study showed ginseng protects folliculogenesis via alteration of hypothalamic- pituitary-gonadal (HPG) axis, induction of proliferation in ovarian somatic cells, reduction of lipid peroxidation, and downregulation of apoptotic markers in the mouse ovary, treated with nicotine. (biomedcentral.com)
  • The 'intrinsic' pathway is activated mainly by non-receptor stimuli, such as DNA damage, ER stress, metabolic stress, UV radiation or growth-factor deprivation. (kegg.jp)
  • Flow cytometry, caspase-3 activity assay in treated monolayers/spheroids and also fluorescence staining and DNA fragmentation in treated monolayers demonstrated apoptotic death mode. (irost.org)
  • Some of these mitochondrial DAMPs share similarities with pathogen-associated molecular patterns (PAMPs) found in bacteria and may be derived from their bacterial ancestors. (nature.com)
  • Administration of prostaglandin E 2 , which was a primary product of arachidonic metabolism, showed no effects against anti-apoptotic effects produced by diclofenac. (elsevierpure.com)
  • Moreover, we discuss the roles of mitochondrial inflammation during cell death and how these processes may potentially be harnessed therapeutically, for instance to improve cancer treatment. (nature.com)
  • Mitochondrial-driven inflammation can enhance the immunogenicity of cell death. (nature.com)
  • Is mitochondrial-driven inflammation during cell death driven by bacterial-like DAMPs? (nature.com)
  • What physiological functions has mitochondrial inflammation during cell death? (nature.com)
  • It may be activated via death receptors (extrinsic pathway) or mitochondrial (intrinsic pathway). (medscape.com)
  • Conversely, a range of pathophysiological insults, including chemotherapy, are thought to cause thrombocytopenia by inducing the apoptotic death of megakaryocytes and their progenitors. (medhelp.org)
  • the intrinsic/mitochondrial apoptotic program is implicated by the data as the main effector pathway in the observed cell death. (igfprotein.com)
  • Prolonged ER stress-mediated cell death, occurring via the intrinsic apoptotic signaling pathway, therefore might be associated with the pathogenesis of FECD. (cardiff.ac.uk)
  • The dose-dependent anti-apoptotic effect of diclofenac did not correlate with the reduction of prostaglandin release. (elsevierpure.com)
  • The effect of MG132-mediated aggresome formation on the UPR and intrinsic pathway and the effect of mitochondrial damage on UPR were also examined. (cardiff.ac.uk)
  • Most cases of ALPS are caused by loss-of-function mutations in components of the FAS apoptotic pathway or extrinsic pathway. (medscape.com)
  • In addition to its importance as a biological phenomenon, defective apoptotic processes have been implicated in a wide variety of diseases. (wikipedia.org)
  • Here, we discuss the importance of these mitochondrial dynamics during neuroinflammation, and how they correlate either with the amelioration or worsening of CNS disease. (frontiersin.org)
  • [ 2 ] Other ALPS-associated genetic defects in the apoptotic pathway and ALPS-like disorders (ALPS-related syndromes) have subsequently been identified. (medscape.com)