Cell Birth, Cell Death

An overview of Chapter 22

By Patty Eneff

Cell Birth

• Cell division implies production of identical daughter cell that do not differ form the parent cells.

• If this were always the case, hundreds of differentiated cells would never be formed.

Differences Occur

• When two Identical daughter cell differ in environmental signals received and diverge into differentiated cells.

• Or daughter cells may divide asymmetrically, and differ in size, shape and/or composition, with different genetic signals.

Stem Cells

• See hand out for diagram

• Give rise to specialized cells such as progenitor cells

Properties of stem cells include Ability to reproduce indefinitely (self renewal)Ability to divide asymmetrically

Patterns of Cell Division

• Unipotent- One cell type

• Pluripotent- More that one kind of cells such as hematopeietic cells that produce various types of blood cells.

• Totipotent- all cells types

Patterns of Cell Division

• Totipotent = zygote (not technically a stem cell) but gives rise to embryonic stem cells.

• The eight cell stage in mammalian cells are totipotent.

• When separated each of the eight cells can give rise to a total organism.

• Eventually divide into germ cells at 64 cell stage, then into ectoderm, mesoderm, and endoderm.

Stem cells

• Give rise to all cells of the body, either directly or indirectly

• Form the basis of cell birth.

Cell Death

Regulated in two fundamentally different ways.

I. Requires signal to stay alive

Absence of signals called trophic factors, activates a cellular suicide program.

II. In developmental context specific signals induce a “murder” program that kills cells.– Cell that are damage by injury e.g.

mechanical damage

exposure to toxic chemicals

Cell Death by Injury

Cells undergo a series of

changes in a process called

necrosis.I. Cells and their organelles swell, because the plasma

membrane’s ability to control the passage of ions and water is damaged.

II. The cell contents leak out, leading to inflammation of surrounding tissues.

Cell Death by Suicide

• Call Apoptosis (Dropping off or falling off as leaves of tree)

– Cell are induced to commit suicide• Shrink• Develop bubble-like blebs on their surface, • Chromatin in their nucleus is degraded• Cytochrome C is release from the mitochondria• Break into small membrane wrapped fragments• Phospholipids (phosphatidylserine) are exposed to surface• Phospholipids is bound by receptors on phagocytic cells• The phagocytic cells release cytokines that inhibit

inflammation.

Differences in Cell Death

Reasons for Apotosis

• Programmed cell death is needed for proper development.– The absorption of the tadpole tail at the time

of metamorphosis into a frog occurs by apotosis

– Formation of fingers and toes of fetus requires apotosis of tissue between them

– Sloughing off of the uterine lining occurs by apotosis

Reasons for Apotosis

• Programmed cell death is needed to destroy cells that represent a threat to the integrity of the organism– Cells infected with viruses– Cells of the immune system

• Cell mediated responses must be removed to prevent attacking self

• Defects in the apototic process are associated with autoimmune disease.

Reasons for Apotosis

• Cells with DNA damageDamaged DNA can cause cancer, birth defects

Cells respond by increasing p53, which is a potential inducer of apotosis.

Radiation and chemicals used in cancer therapy induce apotosis in some types of cancer.

Mechanisms of Apotosis

• External signals = extrinsic pathway– Fas and TNF receptor are integral membrane

proteins.– Binding of the two to complementary death

cell activators transmit a signal to the cytoplasm that leads to activation of caspase 8, which initiates a cascade of caspase activation leading to phagocytosis of the cell.

Mechanisms of Apotosis

• Triggered by internal signals = the intrinsic or mitochondrial pathway.– Bcl-2 on surface of mitochondrial membrane

is present in healthy cells• Damage causes Bcl-2 to release Apaf-1, a related

protein Bax penetrates mitochondrial membrane and cytochrome C leaks out.

• The cytochrome C and Apaf-1 bind to molecules of Caspase 9.

• The resulting complex is called apoptosome.

Addition Apotosis Info

• Caspases are named because they contain a cystine residue and cleave proteins at sites just C-terminal to aspartate residues

• Bad = pro-apoptotic protein – Binds to the anti-apototic protein Bcl-2 and

Bcl-xl– Apoptosis

Summary

• In asymmetrical cell division daughter cells differ from mother cells, as differentiation of stem cells begin the process of cell birth.

• Necessity of cell death protects and helps form organisms.

• Both processes are essential to life.

Questions ????