BIO 224

Intro to Molecular and Cell Biology

Cell Death and Renewal

Carefully regulated to meet needs of entire organism

Balances cell proliferation and maintains constant cell numbers

Provides mechanism to destroy damaged cellsEliminates unwanted cells from tissues

during developmentProvides for maturation of some body

systems

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

Non-Programmed Cell Death

The active process leading to programmed cell death

Chromosomal DNA becomes fragmentedChromatin condenses and nucleus

disintegratesCells shrink and break into membrane-

enclosed apoptotic bodiesApoptotic cells are removed by phagocytosis

Apoptosis

Apoptotic cells display signals on the surface that attract phagocytic cells

Three main genes were identified as responsible for apoptosis in 1986ced-3ced-4ced-9

Caspases carry out activities of apoptosisIn mammalian cells caspases form a multiunit

apoptosome to initiate cell death

Apoptosis

Programmed cell death in C. elegans

Caspase cleavage

Caspase activation

Bcl-2 was identified in mammals as an apoptosis inhibitorAbout 20 different proteins related to Bcl-2 are

produced in mammalsThree 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

Regulation Of Apoptosis

The Bcl-2 family

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

Regulation of Apoptosis

Regulatory interactions between Bcl-2 family members

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

Regulation of Apoptosis

Role of p53 in DNA damage-induced 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

Regulation of Apoptosis

Cell death receptors (Part 1)

Cell death receptors (Part 2)

After embryonic development cells become differentiated to specific tissues and tasks

Many differentiated cells in adult animals are not capable of proliferationIf lost, less differentiated cells proliferate to

replace themSome cells enter the G0 stage and may be

stimulated to proliferate as needed

Adult Tissue Maintenance

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

Differentiated Cell Proliferation

Skin fibroblasts

Endothelial cells

Proliferation of endothelial cells

Liver regeneration

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 organismsThey produce one daughter cell to remain a

stem cell and one to differentiate into the type needed

Stem Cells

Stem cell proliferation

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

Stem Cells

Formation of blood cells

Renewal of the intestinal epithelium (Part 1)

Renewal of the intestinal epithelium (Part 2)

Renewal of the intestinal epithelium (Part 3)

Stem cells of the skin

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

Stem Cells

Muscle satellite cells (Part 1)

Muscle satellite cells (Part 2)

Bone marrow transplantation