L13 Apoptosis

Objectives

  1. Describe the concept of apoptosis

  2. Discuss the difference between necrosis and apoptosis

  3. Outline the differences between intrinsic and extrinsic pathways

  4. Discuss the role of caspases in apoptosis

  5. Outline the importance of apoptosis

  1. What is another name for Apoptosis?

    • Programmed Cell Death

  2. What is Apoptosis

    • Elimination of unwanted or useless cells during the development and other normal biological processes

  3. What are the Physiologic conditions that induces Apoptosis?

    • Embryogenesis

      • removal of excess cells

    • Tissue cells with high turnover rates

      • Skin, Bowels

    • Immune cells

      • Cytokine Depletion

      • Autoreactive T-cells in Thymus development

    • Hormone-dependent Involution

      • shrinking of an organ due to old age or inactivity

        • Endometrium, Ovary, Breasts

  4. What are the Pathologic conditions that induce Apoptosis?

    • Damaged cells via Viruses

    • DNA damage

      • Radiation, Cytotoxic Agents

    • Cancer/Tumors

  5. What are Apoptotic Bodies?

    • Membrane bound vesicles that contain ribosomes and mitochondria

  6. What occurs (Morphology) to the cells that undergo Apoptosis ?

    1. Cell Shrinkage, Organelle Reduction, Mitochondrial Leakage, Membrane Blebbing & Changes

    2. Nuclear Chromatin Condensation

      • peripherally under the Nuclear Membrane

    3. Nuclear and Cytoplasmic Aggregation

    4. Partition (division) of Cytoplasm and Nucleus → Apoptotic Bodies

  7. How does Blebbing directly lead to Apoptosis?

  8. Apoptotic Bodies are Phagocytized by what?

    • Macrophages

  9. T/F: Apoptotic Cell Death induces an inflammatory response

    • False

  10. What components of younger development is Apoptosis used in?

    • Immune systems maturation, Morphogenesis, Neutral development

  11. What components of adult development is Apoptosis used in?

    • Immune privilege, DNA damage and wound repair

  12. What is another name for Necrosis?

    • Accidental Cell Death

  13. What is Necrosis?

    • When cells are exposed to serious physical or chemical injury → swells → ruptured plasma membrane

  14. What are examples that can stimulate Necrosis?

    • Hypoxia and Toxins

  15. When can Necrosis occur?

    • Pathological infections such as Bacterial or Fungal

    • Hypothermia

    • Hypoxia

  16. T/F: Product of Necrotic Cell Death also results in Phagocytosis

    • True

  17. What dysfunctions are seen in both Apoptosis and Necrosis?

    • Profound membrane and Mitochondrial

  18. T/F: Apoptosis and Necrosis can occur in Plants and Animals

    • True, but with different mechanisms

  19. T/F: Necrosis induces an inflammatory response?

    • True due to cellular and nuclear lysis

  20. Differences between Apoptosis and Necrosis

  1. What are examples of development that Apoptosis is utilized in?

    • Formation of fingers and toes of fetuses

    • Sloughing off of the uterus’ inner lining

  2. What is an indication of Apoptosis

    • DNA Laddering

  3. What is DNA Laddering?

    • pattern of DNA fragments that are separated by Gel Electrophoresis

  4. When does p53 induce Gene Activation → Apoptosis?

    • when there is too much cell damage after cell growth arrest between G1 → S of the cell cycle

  5. What are some genes examples that help regulate cell production and apoptosis?

    • Anti-Apoptosis

      • bcl-2 and bcl-xL

        • bcl-2 oncogene over-expression prevents apoptosis

        • localized in mitochondria, nuclear envelope, ER

    • Pro-Apoptosis

      • bax, bcl-xS, bad, bid

  6. How might p53 be involved with regulatory genes for apoptosis?

    • Upregulate Pro-Apoptosis genes such as bax

  7. What are Caspases?

    • site-specific, cysteine Proteases the work as effectors/initiators of the cell death cascade

  8. What is the inactive, precursor form of Caspases

    • Procaspases

      • N-terminal pro domain

      • large subunit (p20)

      • small subunit (p10)

  9. What is the formation of a matured Caspase

    • Heterotetramer with two p20/p10 heterodimers and two active sites

  10. What can result from dysregulated Caspases?

    • CA, autoimmunity, neurodegenerative disorders (excess apoptosis)

  11. What are possible benefits of altering Caspase activity?

    • Therapeutic benefits

  12. Mammalian Caspases can be divided into what 3 functional groups

    • Initiators, Executioner, and Inflammatory

  13. What are examples of Initiator Caspases

    • 2, 8, 9, 10

  14. What are examples of Executionary Caspases

    • 3, 6, 7

  15. What are examples of Inflammatory Caspases

    • 1, 4, 5, 11, 12

  16. What two pathways are triggered to induce cell death with Caspases?

    • Death-Receptor and Mitochondrial Pathways

  17. What is Intrinsic Cell Death?

    • when apoptosis receives activating signals from INSIDE a cell

      • ex. Genotoxic Stress

  18. What is Extrinsic Cell Death?

    • when apoptosis receives activating signals from OUTSIDE a cell

      • ex. Fas ligand

  1. Explain how Fas ligands activate Extrinsic Cell Death