Both intrinsic and extrinsic pathway end up in the common pathway. Extrinsic apoptosis pathway is one of the signal pathways which may trigger the process of programmed cell death namely cell apoptosis. Eldeiry, md, phd summary defects in the extrinsic pathway are linked to several disease states, including cancer. On the other hand, intrinsic pathway can be initiated by dna damage. The most studied cytokine to induce extrinsic pathway of apoptosis is an extracellular messenger protein called tumor necrosis factor tnf. Because trail induces apoptosis in a large proportion of longterm established tumor cell lines, but for as yet unknown reasons is generally not toxic to normal. The two principal pathways of apoptosis are 1 the bcl2 inhibitable or intrinsic pathway induced by various forms of stress like intracellular damage, developmental cues, and external stimuli and 2 the caspase 810 dependent or extrinsic pathway initiated by the engagement of death receptors the caspase 810 dependent or extrinsic pathway. Coagulation cascade has two pathways known as intrinsic and extrinsic pathway. A small molecule that induces intrinsic pathway apoptosis. As tumors frequently acquire mutations that make them resistant to apoptosis induction via the intrinsic pathway, targeting the extrinsic apoptosis pathways is attractive in cancer therapy.
We start off by taking a look at the important role apoptosis plays in growth and development. Pharmacologic manipulation of the extrinsic pathway holds exciting promise. Both intrinsic and extrinsic pathways belong to secondary hemostasis mechanisms. Both extrinsic and intrinsic pathways lead to activation of caspases, the proteases that cleave many key protein targets inside.
The beststudied influenza virus inducers of apoptosis are dsrna, ns1, na, and a newly described gene product pb1f2. Intrinsic apoptosis is a response to internal damage eg. Multiple influenza virus factors have been identified that can activate intrinsic or extrinsic apoptotic induction pathways. In both pathways the cell does itself the difference is in the reason. In this pathway, mitochondria are critical for the.
Apoptosis can therefore occur either through an intrinsic pathway, in which signals from within the cell activate the process, or through an extrinsic pathway where death signals from outside the cell are received and processed by the cell to activate apoptosis. Difference between intrinsic and extrinsic pathways in. Difference between intrinsic and extrinsic pathway in. Process and regulation of intrinsic apoptosis pathway. Activated caspase3induced apoptosis pathways, including extrinsic caspase8mediated and intrinsic caspase9mediated pathways, in salmonellainfected macrophages were verified. While the ability of caspases to selfcleave provides one level of such feedback activity, we find that this feedback extends to cross activation between both the extrinsic and intrinsic pathways, with specific activation of either extrinsic or intrinsic apoptosis leading to near simultaneous activation of both caspase8 and 9 in all. The raptinal mechanism involves mitochondrialmediated intrinsic pathway. Thp1 cells with dysfunction of tlr4 and tlr5 and salmonella spi1 and spi2 mutants were constructed to identify the roles of the genes associated with programmed cell. Deep sleep music247, sleep therapy, insomnia, sleep meditation, calm music, study, relax, sleep body mind zone 8,902 watching live now. Taken together, all the results demonstrated that both intrinsic and extrinsic apoptosis pathways were activated by oleandrin in inducing the apoptosis of os cells. This 3d medical animation explains the functioning of the extrinsic and intrinsic apoptotic pathways.
Coordination of intrinsic, extrinsic, and endoplasmic. The mitochondria, as the crosstalk organelles, can connect the different apoptosis pathway. Pathways apoptosis can be triggered in a cell through either the extrinsic pathway or the intrinsic pathway. These data suggested that oleandrin could also induce the activation of intrinsic apoptosis pathway in os cells that are independent of the extrinsic pathway. There are two major apoptosis pathways distinguished according to whether caspases are involved or not. While the intrinsic and extrinsic pathways are different processes, they ultimately converge on the same terminal. This is the point at which caspases become enzymatically active. The intrinsic pathway mainly triggers apoptosis in response to internal stimuli.
The extrinsic pathway involves death receptors, death inducing signaling complex and caspase activation. It is triggered via extrinsic or intrinsic pathways. Tnf is so named because it was first discovered as a protein factor which induces cell death in cancerous cells. Execution phase the intrinsic and extrinsic pathways converge to a. Apoptosis intrinsic and extrinsic pathways youtube.
Even though the signaling cascades of extrinsic and intrinsic pathways are separate, there is always crosstalk between these two pathways. Therapeutic small molecules target inhibitor of apoptosis. The intrinsic cell death pathway involves the initiation of apoptosis as a result of a disturbance of intracellular homeostasis. Potential of apoptotic pathwaytargeted cancer therapeutic. In the intrinsic pathway cellular stress, once detected, causes the cell to. These activated caspases cause chromosomal dna fragmentation into internucleosomal fragments, degradation of cytoskeleton and nuclear proteins, and crosslinking of proteins 5,11. The intrinsic pathway is initiated by, for example, chemotherapy andor radiotherapy, and the extrinsic pathway is initiated by ligandinduced. Apoptosis is known as a physiological process of cell deletion and is also a process of programmed cell death, resulting in morphological change and dna fragmentation. Importance, vs necrosis, cancer, and its intrinsic pathway. Currently there is no evidence for influenza virus directly accessing the apoptosis execution factors. Trail is a type ii transmembrane cytokine and a potent inducer of apoptosis in cancer cells. A free powerpoint ppt presentation displayed as a flash slide show on id. Apoptosis can be induced by several means activating intrinsic or extrinsic pathways.
The process of apoptosis is controlled by diversity cell signals pathway and involved in regulation of cell fate death or survival. The cellular basis of disease cell injury 3 apoptosis and necrosis cellular aging. Apoptosis is triggered by chronological activation of caspase family via two distinct but congregating pathways known as intrinsic and extrinsic pathways. Key difference intrinsic vs extrinsic pathways in blood clotting blood clotting is an important process to stop bleeding. The extrinsic pathway involves engagement of particular death receptors that belong to the tumor tnfr tumor necrosis factor receptor family and, through the formation of the disc deathinducingsignalingcomplex, leads to a cascade of activation of. Regarding apoptosis, there are two general pathways, the extrinsic pathways and the intrinsic pathways, depending on whether the molecular factor that initiates the death pathway is extracellular or intracellular. The intrinsic signaling pathway for programmed cell death involves nonreceptormediated intracellular signals, inducing activities in the mitochondria that initiate apoptosis.
Apoptosis, or programmed cell death, is important in development, aging, and disease. The external stimuli for the apoptosis in most of the cases will be a cytokine. Two primary death signaling cascades, the extrinsic and intrinsic pathways, have been extensively characterized fig. What is the difference between intrinsic and extrinsic. Apoptosis is characterized by the following biochemical changes. Difference between extrinsic pathway and intrinsic pathway. It is a complicated process which occurs via series of activation processes collectively called coagulation cascade. Specific markers of the extrinsic pathway of apoptosis ie, tnfr1, casp8, and casp10 are prominently induced in the cotreatment samples of both patients, and those of the intrinsic pathway ie, bax seem to be somewhat differentially expressed in the cotreatment samples between the 2 patients. Apoptosis can be initiated by one of two separate pathways.
The exact mechanism of intrinsic and extrinsic pathways of apoptosis will be discussed later. Apoptosis can be executed through a mitochondriadependent intrinsic and a death receptordependent, mitochondriaindependent extrinsic pathway. The downstream effector molecules for both pathways that mediate apoptosis include caspases, a group of cysteine proteases that cleave a variety of cytoplasmic and nuclear substrates. Difference between intrinsic and extrinsic pathway in blood clotting definition. Fas expressed on cell surface linked to death domain. Caspase 8 can directly induce apoptosis or activates caspase 3 or bid, which lead to apoptosis. Apoptosis pathways there are two pathways that can initiate apoptosis in a cell. To characterize whether raptinalinduced apoptosis occurs through the intrinsic or extrinsic pathway, the kinetics of cytochrome c release were determined by fractionating between cytosolic or mitochondrial proteins using selective permeabilization with digitonin combined with. Intrinsic and extrinsic pathways are connected via caspase810 by cleaving bid,a bh3only member of the bcl2 family, that destabilizes outer mitochondrial membrane by. The extrinsic and intrinsic apoptosis pathways both lead to cell death execution via caspase3 andor caspase7 cleavage 2. A framework for druginduced apoptosis can now be described in which a balance exists between intrinsic and extrinsic survival signals and drug.
Efficient apoptosis requires feedback amplification of. Both intrinsic and extrinsic pathways are involved in the formation of prothrombin activator and factor x. The extrinsic pathway is initiated through the stimulation of the transmembrane death receptors, such as the fas receptors, located on the cell membrane. Extrinsic pathway intrinsic pathway major players in apoptosis. Tumor necrosis factorrelated apoptosisinducing ligand. It is thought that the intrinsic apoptotic pathway is more important in cancer. Crosstalk between extrinsic and intrinsic cell death. Extrinsic apoptosis pathway signalling easybiologyclass. Stimuli for the intrinsic pathway include viral infections or damage to the cell by toxins, free radicals, or radiation. Activation of apoptosis by salmonella pathogenicity island. Mitochondria as central regulators of intrinsic apoptosis pathways besides amplifying and mediating extrinsic apoptotic pathways, mitochondria also play a central role in the integration and propagation of death signals originating from inside the cell such as dna damage, starvation, as well as those induced by chemotherapeutic drug.
The intrinsic apoptosis pathway induces apoptosis by directly activating caspase3 or by cleaving bid bh3 interacting domain death agonist, resulting in mitochondrial dysfunction and subsequent release of cytochrome c and. The explosion of interest in apoptosis amongst cancer biologists has been underpinned by the hope that a mechanistic understanding of cell death will inform our understanding of tumour drug resistance. Both of these pathways end with a final common effector pathway, known as the execution phase. Regulation of intrinsic and extrinsic apoptotic pathways. Major apoptotic mechanisms and genes involved in apoptosis.1639 1592 1340 1458 363 48 733 1037 873 277 288 582 1180 1204 670 1558 207 767 1519 221 233 1581 697 1129 1557 489 1005 268 882 539 934 1496 580 744 532 449 885