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Lecture 1.2a - Cell injury and cell death 2

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What is the primary trigger for the intrinsic pathway of apoptosis?

Most commonly irreparable DNA damage

What is the primary characteristic of apoptosis?

It is an energy-dependent active process

What happens to the nuclear DNA during apoptosis?

It is degraded by enzymes

What is the role of the p53 protein in the intrinsic pathway of apoptosis?

It is inactivated, resulting in the outer mitochondrial membrane becoming leaky

What is the final step in the clearance of apoptotic bodies?

Degradation takes place within the phagocytes

What is the primary function of apoptosis during embryogenesis?

To remove excess tissue and sculpt organs

Which of the following is an example of physiological apoptosis?

Hormone-controlled involution of breast gland epithelium after lactation

What is the difference between oncosis/necrosis and apoptosis?

Oncois/necrosis is characterized by cellular swelling, while apoptosis is characterized by cellular shrinkage

What is the role of caspases in apoptosis?

To control and mediate apoptosis by causing cleavage of DNA and proteins

What is the role of TNFalpha in the extrinsic pathway of apoptosis?

It is a cytokine secreted by T killer cells that binds to death receptors

What is the result of cytochrome C release from the mitochondria in the intrinsic pathway of apoptosis?

Activation of caspases

What is the characteristic of apoptosis in terms of the number of cells affected?

It affects a single cell or a small group of cells

What is the initiating signal for the intrinsic pathway of apoptosis?

A signal from within the cell

What is the characteristic of the membrane during apoptosis?

It is maintained, preserving cellular integrity

Study Notes

Apoptosis: Programmed Cell Death

  • Apoptosis is a programmed cell death, an active process that requires energy
  • Characterized by shrinkage, induced by a regulated intracellular program
  • Enzymes are activated to degrade nuclear DNA and proteins, maintaining membrane integrity
  • Affects a single cell or group of cells, with a characteristic microscopic appearance
  • Lysosomal enzymes are not involved, and the process is quick, taking only a few hours

Physiological Apoptosis

  • Occurs to maintain a steady state
  • During hormone-controlled involution, such as in breast gland epithelium after lactation
  • During embryogenesis, for removal of tissue and organ sculpting

Pathological Apoptosis

  • Occurs in cytotoxic T cell killing of virus-infected cells
  • Removal of neoplastic cells
  • In response to cell damage, particularly with damaged DNA
  • In graft vs host disease

Initiation and Execution of Apoptosis

  • Triggered by two mechanisms: intrinsic and extrinsic pathways
  • Both pathways result in activation of caspases, enzymes that control and mediate apoptosis
  • Caspases cause cleavage of DNA and proteins of the cytoskeleton

Intrinsic Pathway

  • Initiated by signals from within the cell
  • Triggers include irreparable DNA damage and withdrawal of growth factors or hormones
  • p53 protein is inactivated, leading to leaky outer mitochondrial membrane
  • Cytochrome C is released, causing activation of caspases

Extrinsic Pathway

  • Initiated by extracellular signals
  • Triggers include cells that are a danger, such as tumor cells or virus-infected cells
  • One of the signals is TNFalpha, secreted by T killer cells
  • TNFalpha binds to cell membrane receptor, resulting in activation of caspases

Clearance of Apoptotic Bodies

  • Both intrinsic and extrinsic pathways cause cells to shrink and break up into apoptotic bodies
  • Apoptotic bodies express proteins on their surface, allowing recognition by phagocytes or neighboring cells
  • Finally, degradation takes place within the phagocytes

Apoptotic vs Necrotic Cells

  • Apoptotic cells: programmed cell death, shrinkage, and maintenance of membrane integrity
  • Necrotic cells: unprogrammed cell death, cell swelling, and loss of membrane integrity

Learn about programmed cell death, a regulated intracellular process involving enzyme activation, DNA degradation, and membrane integrity maintenance. Understand the characteristics of apoptosis and its effects on single cells or groups of cells.

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