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
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
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
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
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
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
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
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
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