Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout Mice
Under stress conditions, cells in living tissue die by apoptosis or necrosis depending on the activation of the key molecules within a dying cell that either transduce cell survival or death signals that actively destroy the sentenced cell. Multiple extracellular (pH, heat, oxidants, and detergents)...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/128076 |
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| author | José Belizário Luiz Vieira-Cordeiro Sylvia Enns |
| author_facet | José Belizário Luiz Vieira-Cordeiro Sylvia Enns |
| author_sort | José Belizário |
| collection | DOAJ |
| description | Under stress conditions, cells in living tissue die by apoptosis or necrosis depending on the activation of the key molecules within a dying cell that either transduce cell survival or death signals that actively destroy the sentenced cell. Multiple extracellular (pH, heat, oxidants, and detergents) or intracellular (DNA damage and Ca2+ overload) stress conditions trigger various types of the nuclear, endoplasmic reticulum (ER), cytoplasmatic, and mitochondrion-centered signaling events that allow cells to preserve the DNA integrity, protein folding, energetic, ionic and redox homeostasis, thus escaping from injury. Along the transition from reversible to irreversible injury, death signaling is highly heterogeneous and damaged cells may engage autophagy, apoptotic, or necrotic cell death programs. Studies on multiple double- and triple- knockout mice identified caspase-8, flip, and fadd genes as key regulators of embryonic lethality and inflammation. Caspase-8 has a critical role in pro- and antinecrotic signaling pathways leading to the activation of receptor interacting protein kinase 1 (RIPK1), RIPK3, and the mixed kinase domain-like (MLKL) for a convergent execution pathway of necroptosis or regulated necrosis. Here we outline the recent discoveries into how the necrotic cell death execution pathway is engaged in many physiological and pathological outcome based on genetic analysis of knockout mice. |
| format | Article |
| id | doaj-art-74028c95347c4b1190939e9ea910f16b |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-74028c95347c4b1190939e9ea910f16b2025-02-03T05:43:50ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/128076128076Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout MiceJosé Belizário0Luiz Vieira-Cordeiro1Sylvia Enns2Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, BrazilDepartment of Animal Science, Federal Rural University of the Semiarid Region, 59625-900 Mossoró, RN, BrazilDepartment of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, BrazilUnder stress conditions, cells in living tissue die by apoptosis or necrosis depending on the activation of the key molecules within a dying cell that either transduce cell survival or death signals that actively destroy the sentenced cell. Multiple extracellular (pH, heat, oxidants, and detergents) or intracellular (DNA damage and Ca2+ overload) stress conditions trigger various types of the nuclear, endoplasmic reticulum (ER), cytoplasmatic, and mitochondrion-centered signaling events that allow cells to preserve the DNA integrity, protein folding, energetic, ionic and redox homeostasis, thus escaping from injury. Along the transition from reversible to irreversible injury, death signaling is highly heterogeneous and damaged cells may engage autophagy, apoptotic, or necrotic cell death programs. Studies on multiple double- and triple- knockout mice identified caspase-8, flip, and fadd genes as key regulators of embryonic lethality and inflammation. Caspase-8 has a critical role in pro- and antinecrotic signaling pathways leading to the activation of receptor interacting protein kinase 1 (RIPK1), RIPK3, and the mixed kinase domain-like (MLKL) for a convergent execution pathway of necroptosis or regulated necrosis. Here we outline the recent discoveries into how the necrotic cell death execution pathway is engaged in many physiological and pathological outcome based on genetic analysis of knockout mice.http://dx.doi.org/10.1155/2015/128076 |
| spellingShingle | José Belizário Luiz Vieira-Cordeiro Sylvia Enns Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout Mice Mediators of Inflammation |
| title | Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout Mice |
| title_full | Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout Mice |
| title_fullStr | Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout Mice |
| title_full_unstemmed | Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout Mice |
| title_short | Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout Mice |
| title_sort | necroptotic cell death signaling and execution pathway lessons from knockout mice |
| url | http://dx.doi.org/10.1155/2015/128076 |
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