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Cell Death and Renewal

Cell Death and Renewal. BIO 224 Intro to Molecular and Cell Biology. Programmed Cell Death. Carefully regulated to meet needs of entire organism Balances cell proliferation and maintains constant cell numbers Provides mechanism to destroy damaged cells

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Cell Death and Renewal

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  1. Cell Death and Renewal BIO 224 Intro to Molecular and Cell Biology

  2. Programmed Cell Death • Carefully regulated to meet needs of entire organism • Balances cell proliferation and maintains constant cell numbers • Provides mechanism to destroy damaged cells • Eliminates unwanted cells from tissues during development • Provides for maturation of some body systems

  3. Non-Programmed Cell Death • Cell death resulting from acute damage or injury has unpredictable consequences • Cells that die accidentally swell and lyse, leading to inflammation • Tissues may become damaged due to non-apoptosis-mediated cell death

  4. Apoptosis • The active process leading to programmed cell death • Chromosomal DNA becomes fragmented • Chromatin condenses and nucleus disintegrates • Cells shrink and break into membrane-enclosed apoptotic bodies • Apoptotic cells are removed by phagocytosis

  5. Apoptosis • Apoptotic cells display signals on the surface that attract phagocytic cells • Three main genes were identified as responsible for apoptosis in 1986 • ced-3 • ced-4 • ced-9 • Caspases carry out activities of apoptosis • In mammalian cells caspases form a multiunit apoptosome to initiate cell death

  6. Programmed cell death in C. elegans

  7. Caspasecleavage

  8. Caspaseactivation

  9. Regulation Of Apoptosis • Bcl-2 was identified in mammals as an apoptosis inhibitor • About 20 different proteins related to Bcl-2 are produced in mammals • Three functional groups have been identified, one group of inhibitors and two groups of proapoptotic proteins • Defects in bcl-2 were found in many cases of human b-cell lymphomas

  10. The Bcl-2 family

  11. Regulation of Apoptosis • Cellular fate depends on the balance of pro-apoptotic and anti-apoptotic proteins • Bcl-2 family proteins act at mitochondria, releasing cytochrome c • Caspases are activated by cytochrome c to intiate apoptosis • IAP family proteins also regulate caspases by direct inhibition or targeting them for destruction

  12. Regulatory interactions between Bcl-2 family members

  13. Regulation of Apoptosis • Cell signaling pathways regulate apoptosis by inhibition or initiation • Elimination of damaged cells is an important role of apoptosis • Mediation of apoptosis in response to DNA damage is through p53 • Nerve cells are spared from apoptosis due to receipt of NGF signals from target cells

  14. Role of p53 in DNA damage-induced apoptosis

  15. Regulation of Apoptosis • Some proteins signal apoptosis by activation of cell-surface receptors directly responsible for its initiation • Members of the tumor necrosis factor (TNF) family signal apoptosis in a number of cell types

  16. Cell death receptors (Part 1)

  17. Cell death receptors (Part 2)

  18. Adult Tissue Maintenance • After embryonic development cells become differentiated to specific tissues and tasks • Many differentiated cells in adult animals are not capable of proliferation • If lost, less differentiated cells proliferate to replace them • Some cells enter the G0 stage and may be stimulated to proliferate as needed

  19. Differentiated Cell Proliferation • Fibroblasts are found in connective tissues secreting collagen • They are stimulated to repair tissues if necessary • Blood vessel endothelial cells proliferate to form new vessels as needed for growth and repair • Epithelial cells of some organs may proliferate to replace damaged tissue

  20. Skin fibroblasts

  21. Endothelial cells

  22. Proliferation of endothelial cells

  23. Liver regeneration

  24. Stem Cells • Most fully differentiated adult cells can no longer divide • Subpopulations of self-renewing stem cells present in adult tissues may divide to produce necessary cells • Stem cells are important in maintenance of tissues and organs in adult organisms • They produce one daughter cell to remain a stem cell and one to differentiate into the type needed

  25. Stem cell proliferation

  26. Stem Cells • Adult stem cell examples are well characterized • Hematopoietic stem cells proliferate to produce blood cells to maintain differentiated populations • Intestinal epithelial cells proliferate to renew the lining • Epidermal skin stem cells renew the epidermis completely every two weeks

  27. Formation of blood cells

  28. Renewal of the intestinal epithelium (Part 1)

  29. Renewal of the intestinal epithelium (Part 2)

  30. Renewal of the intestinal epithelium (Part 3)

  31. Stem cells of the skin

  32. Stem Cells • Skeletal muscle stem cells repair tissues in contrast to continual replacement • Stem cells have been identified but not well characterized in other adult tissues including the brain, heart, lung, and liver • Adult stem cells of one tissue type may be stimulated to produce tissues of another type • Stem cells’ ability to repair tissues allow them to be used clinically for treatment of disease

  33. Muscle satellite cells (Part 1)

  34. Muscle satellite cells (Part 2)

  35. Bone marrow transplantation

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