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Related Concept Videos

Necrosis01:16

Necrosis

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Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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Apoptosis01:30

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Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

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Execution of RIPK3-regulated necrosis.

Zhenyu Cai1, Zheng-Gang Liu1

  • 1Center for Cancer Research; National Cancer Institute; National Institutes of Health , Bethesda, MD USA.

Molecular & Cellular Oncology
|June 17, 2016
PubMed
Summary

Necroptosis, a regulated cell death, is triggered by various receptors and mediated by RIP1 and RIP3 kinases. The MLKL protein is essential for executing this process, involving ions and reactive oxygen species.

Keywords:
MLKLRIP3ROScalciumnecroptosissodium

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Immunology

Background:

  • Necroptosis is a programmed form of necrosis.
  • It is crucial in immunity and disease.
  • Key molecular players are being identified.

Purpose of the Study:

  • To elucidate the molecular mediators of necroptosis.
  • To understand the signaling pathways involved in regulated necrosis.

Main Methods:

  • Analysis of receptor-interacting protein 1 (RIP1) and RIP3 kinase activity.
  • Investigation of the role of the mixed lineage kinase-like (MLKL) protein.
  • Examination of upstream receptor signaling pathways.

Main Results:

  • Receptor-interacting protein 1 (RIP1) and RIP3 kinases mediate necroptosis.
  • The mixed lineage kinase-like (MLKL) protein functions downstream of RIP1/RIP3.
  • Diverse receptors can initiate the necroptotic pathway.

Conclusions:

  • Identification of key mediators like RIP1, RIP3, and MLKL is critical.
  • Understanding necroptosis mechanisms is vital for therapeutic strategies.
  • Further research into associated factors like ions and ROS is warranted.