Video Experimental Relacionado
Updated: Jan 3, 2026
05:29
Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry
Published on: March 24, 2023
5.3K
La actividad de la caspasa-8 determina la plasticidad entre las vías de muerte celular
Kim Newton1, Katherine E Wickliffe2, Allie Maltzman2
1Department of Physiological Chemistry, Genentech, South San Francisco, CA, USA. knewton@gene.com.
Nature
|November 15, 2019
Resumen
La caspasa-8 inactiva (CASP8) desencadena una inflamación letal mediante la activación de las vías de la caspasa-1 y la caspasa-11, incluso cuando la necroptosis está bloqueada. Esto revela una plasticidad inesperada en las vías de muerte celular.
Área de la Ciencia:
- Biología celular
- Inmunología
- Biología molecular
Sus antecedentes:
- La caspasa-8 tiene una doble función, mediando la apoptosis y suprimiendo la necroptosis.
- Los ratones que carecen de caspasa-8 funcional muestran letalidad embrionaria, lo que sugiere una función de andamio pro-muerte.
Objetivo del estudio:
- Para investigar la función pro-muerte del andamio de la caspasa-8 inactiva.
- Para aclarar los mecanismos moleculares subyacentes a la letalidad observada en ratones con caspasa-8 inhibida y MLKL.
Principales métodos:
- Se utilizaron modelos de ratón modificados genéticamente (Casp8 ((C362A), Mlkl-/-, Casp1-/-, Asc-/-, Casp11-/).
- Se analizó la escisión dependiente de la caspasa-1 de GSDMD y las caspasas aguas abajo.
- Se examinó la formación de partículas ASC y la regulación de la caspasa-11 en los tejidos intestinales.
Principales resultados:
- La caspasa-8 inactiva (CASP8 ((C362A)) indujo la formación de manchas ASC y la escisión dependiente de la caspasa-1 de GSDMD, caspasa-3 y caspasa-7 en ratones con deficiencia de MLKL.
- Caspase-1 y ASC fueron críticos para el fenotipo letal perinatal.
- El aumento de la caspasa-11 también contribuyó a la letalidad.
- Una función independiente de la necroptosis de RIPK3 también contribuyó a la letalidad.
Conclusiones:
- La caspasa-8 inactiva posee una función de andamiaje pro-muerte que activa las caspasas inflamatorias (caspasa-1 y caspasa-11).
- Esta vía implica la formación de manchas ASC y la escisión de GSDMD, lo que lleva a la letalidad perinatal.
- El estudio revela una plasticidad significativa en las vías de muerte celular, con implicaciones para comprender las enfermedades inflamatorias.
Videos de Conceptos Relacionados
01:24Caspases
13.6K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
13.6K
01:17The Extrinsic Apoptotic Pathway
7.9K
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...
7.9K
01:31The Intrinsic Apoptotic Pathway
8.1K
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...
8.1K
01:30Overview of Cell Death
9.2K
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.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
9.2K
01:30Apoptosis
13.8K
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...
13.8K
01:18Autophagic Cell Death
4.2K
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.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.2K