Caspase activation

Definition

Caspase activation refers to the process by which caspases, a family of cysteine proteases, are activated to carry out the execution phase of apoptosis, or programmed cell death. This activation is crucial for the dismantling of cellular components in a controlled manner, ensuring that dying cells do not provoke an inflammatory response. The activated caspases play a pivotal role in the cleavage of various substrates leading to morphological changes associated with apoptosis, such as cell shrinkage and membrane blebbing.

5 Must Know Facts For Your Next Test

1. Caspase activation is initiated by either extrinsic or intrinsic apoptotic signals, leading to a cascade of events that ultimately activate executioner caspases.
2. Executioner caspases (such as caspase-3) are responsible for the cleavage of key proteins that result in the characteristic features of apoptosis, including DNA fragmentation and cytoskeletal breakdown.
3. Caspase-8 is typically activated in the extrinsic pathway through death receptor signaling, while caspase-9 is activated in the intrinsic pathway through cytochrome c release from mitochondria.
4. Caspases also play roles in inflammation; for instance, some caspases can activate pro-inflammatory cytokines, linking apoptosis to inflammatory responses.
5. Dysregulation of caspase activation can lead to various diseases, including cancer, where evasion of apoptosis allows malignant cells to survive longer than they should.

Review Questions

• How does the activation of caspases initiate the process of apoptosis, and what are the key differences between the intrinsic and extrinsic pathways?
  • Caspase activation initiates apoptosis by triggering a cascade where inactive precursors (pro-caspases) are cleaved into active forms. In the intrinsic pathway, internal stressors like DNA damage lead to mitochondrial release of cytochrome c, activating caspase-9. In contrast, the extrinsic pathway involves external signals that bind to death receptors on the cell surface, activating caspase-8. Both pathways converge on executioner caspases that carry out cell death.
• Discuss the role of executioner caspases in apoptotic cell death and their specific substrates that are cleaved during this process.
  • Executioner caspases, such as caspase-3, play a central role in executing apoptosis by cleaving a variety of substrates. These substrates include proteins involved in maintaining cellular structure and function, such as PARP (poly(ADP-ribose) polymerase), which is critical for DNA repair. The cleavage of these substrates leads to characteristic apoptotic changes like chromatin condensation and membrane blebbing, ensuring the cell's controlled demise.
• Evaluate how dysregulation of caspase activation can contribute to disease states such as cancer or neurodegenerative disorders.
  • Dysregulation of caspase activation can have significant implications for disease states like cancer and neurodegenerative disorders. In cancer, cells may evade apoptosis due to dysfunctional caspase pathways or increased expression of anti-apoptotic proteins, allowing tumor cells to survive and proliferate uncontrollably. Conversely, excessive or inappropriate activation of caspases can lead to unwanted cell death in neurodegenerative disorders like Alzheimer's disease. Understanding these mechanisms highlights potential therapeutic targets for treating these diseases.

Related terms

Apoptosis: A regulated process of cell death characterized by specific morphological and biochemical features, essential for maintaining tissue homeostasis.

Caspases: A family of cysteine proteases that are instrumental in the execution of apoptosis and inflammation, existing as inactive precursors (pro-caspases) that require activation.

Intrinsic pathway: A pathway of apoptosis triggered by internal signals, such as DNA damage, that leads to mitochondrial release of cytochrome c and subsequent caspase activation.