Caspase activation

Definition

Caspase activation refers to the process through which caspases, a family of cysteine proteases, are activated to execute apoptosis, or programmed cell death. This activation is a critical step in the intrinsic and extrinsic pathways of apoptosis, leading to cellular disassembly and ultimately cell death. The controlled activation of caspases ensures that cells can remove damaged or unwanted cells effectively, playing a vital role in tissue homeostasis and development.

5 Must Know Facts For Your Next Test

1. Caspases exist as inactive precursors known as procaspases, which undergo proteolytic cleavage to become active enzymes during apoptosis.
2. There are two main types of caspases: initiator caspases (like caspase-8 and caspase-9) that start the apoptotic process and executioner caspases (like caspase-3, -6, and -7) that carry out the death program.
3. Caspase activation can be influenced by various cellular signals, including growth factor withdrawal, DNA damage, and viral infections.
4. Once activated, caspases cleave specific substrates in the cell, leading to characteristic changes associated with apoptosis such as cell shrinkage, nuclear fragmentation, and membrane blebbing.
5. Caspases are not only involved in apoptosis but also play roles in inflammation and other cellular processes, highlighting their importance beyond just cell death.

Review Questions

• How do initiator and executioner caspases differ in their roles during apoptosis?
  • Initiator caspases, such as caspase-8 and caspase-9, act at the beginning of the apoptotic signaling cascade. They are responsible for receiving the initial signals that trigger apoptosis and then activate executioner caspases. Executioner caspases, like caspase-3, -6, and -7, are downstream components that carry out the death program by cleaving specific cellular substrates to dismantle the cell's structure and function.
• Discuss how the intrinsic pathway of apoptosis leads to caspase activation and its implications for cellular health.
  • The intrinsic pathway of apoptosis is initiated by internal stress signals like DNA damage or oxidative stress. These signals lead to mitochondrial outer membrane permeabilization (MOMP), causing the release of cytochrome c into the cytosol. Cytochrome c then interacts with Apaf-1 to form an apoptosome, which activates initiator caspase-9. This cascade culminates in the activation of executioner caspases that execute the death program. This process is essential for maintaining cellular health by eliminating potentially harmful cells.
• Evaluate the broader implications of dysregulated caspase activation in diseases such as cancer and neurodegeneration.
  • Dysregulated caspase activation can lead to significant health issues. In cancer, impaired apoptosis allows abnormal cells to survive and proliferate, contributing to tumor growth. Conversely, excessive or inappropriate caspase activation can result in neurodegenerative diseases by triggering cell death in healthy neurons. Understanding these mechanisms can help develop therapeutic strategies targeting these pathways, highlighting the crucial balance required for maintaining cellular homeostasis.

Related terms

Apoptosis: A form of programmed cell death that occurs in a regulated manner, characterized by specific morphological changes and energy-dependent processes.

Cysteine Proteases: A class of proteolytic enzymes that use a cysteine residue in their active site to cleave peptide bonds, including the caspases involved in apoptosis.

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