cell cycle and apoptosis Flashcards
What is the frequency of cell division like? (Cycle time)
Embryo- 20 mins
Skin- 12-24hrs
Liver- years
What is mitosis?
Results in 2 identical daughter cells
DNA duplicated exactly and divided equally
What is the cell cycle?
Mitotic phase (cell division) Interphase- ~ Gap1- cell grows ~ S- replication of DNA ~ Gap2- cell prepares to divide
GO- cells that cease division
What are the stages of mitosis?
Interphase
Prophase- condensation of DNA into chromosomes and attach to spindle structure (microtubules)
Prometaphase- nuclear envelope breaks down
Metaphase- chromosomes lined up in an equatorial plate
Anaphase- tension applied to chromosomes (molecular motors) pull them apart to opposite poles
Telophase- cells separate (contractile actin ring)- cytokinesis
How is the cell cycle regulated?
Extra and intracellular signals influence
Checkpoints at different stages
~critical points- G1, G2 and M phase
G1- checks environment is right, enough nutrients, no damage etc
G2- complete replication correct
M- alignment of chromosomes correct
What is the nuclear fusion experiment (Rao and Johnson)?
Fuses nuclei together to see the influence of different phases on eachother
Conclusion- mitotic nuclei release mitosis-promoting factor that affects all interphase nuclei to drive it forward
What are cyclins?
Proteins that control cell cycle
Levels rise and fall with differ t stages
What are cyclin dependent kinases?
Phosphorylation proteins that control cell cycle
Levels fairly constant
CDK binds to appropriate cyclin
Activity controlled by cyclin dependent kinase inhibitors
What regulates the cell cycle?
Cyclin and CDK synthesis
Cyclin degradation, CDK phosphorylation, CDK inhibition
Promoting factor= Cyclin + CDK
~phosphorylates and activates proteins inv in chromatin condensation, nuclear envelope breakdown, spindle assembly and own destruction
What is MPF?
Mitosis promoting factor
At G2/M checkpoint
What is APC?
Anaphase promoting complex
Degraded cyclin B
At spindle checkpoint
How might extracellular signals promote cell division?
Growth factor binds to cell surface receptor
Changes conformation slightly
Activates protein kinase cascade
Translocated to nucleus
Binds to DNA and promotes transcription, translation OR cyclin dependent kinase
Cell division
What is G0?
Cells permanently/temporarily leave cell cycle
Most cells in G0
Resting or quiescent
Can do other things eg. secrete
~Terminal differentiation- permanent eg. Keratinocytes, lymphocytes
~Cells that can re-enter cycle- in response to signals eg. Liver
What is cell cycle in disease?
Dysregulated cell growth- cancer
Many cell cycle regulatory genes are TSGs
Cancer treatments target rapidly growing cells-
~high energy radiation
~chemotherapy targets DNA replication, mitosis and cytokinesis (drugs prevent formation of new blood vessels)
What is the p53 TSG?
Guardian of genome If DNA damaged, p53- ~initiate DNA repair ~arrest cell cycle ~initiate apoptosis
p53 is mutated in 50% cancers
Defective p53 allows abnormal cells to proliferate
How can the cell cycle be used in oral pathology?
Mitosis visible under haematoxylin and eosin
Number- indicates active growth eg. Ulcer healing
Location- eg. Suprabasal may indicate pathology
What do apoptosis?
Programmed cell death
Essential- normal development
Destroys cells that are threat (virus infected, immune, DNA damage)
Initiated by withdraw of positive signals (eg growth factors) or receipt of negative signals (eg UV)
How does apoptosis happen?
Cells shrink slightly
Nuclear breakdown into fragments
Cell breaks down into smaller membrane bound remains
These are phagocytosed
What is the difference between apoptosis and necrosis?
Apoptosis- controlled, energy dependent, cells shrink, membrane intact, non-inflam, no scarring, small cell groups, nuclear fragmentation
Necrosis- uncontrolled, no ATP required, cell swells, no membrane integrity, inflam, scarring, large cell group, nuclear dissolution, pathological
What is intrinsic apoptosis?
Controlled by integrity of mitochondrial membrane
If not there, cytochrome C is released* into cytoplasm and combines w other protein
Activates- cascade of caspase activation
Bcl-2 (b cell lymphoma) stops this formation*
What is extrinsic apoptosis?
Ligand (eg. FasL) binds to cell surface receptor (eg. Fas)
This combined w adaptor molecules (eg. FADD)
Activates- cascade of caspase activation
What are caspases?
Proteolytic enzymes (cysteine proteases)
Effectors of apoptosis
Present as inactive proenzyme (zymogen)
Activation cascade (caspase 9 activates caspase 2,3,6,7,8,10)
Numerous substrates (eg. Cytoskeleton, nuclear membrane)
What is apoptosis in disease?
Avoidance in cancer eg. Bcl-2
HPV inactivates p53
EBV produce protein similar to Bcl-2
Melanoma inhibits expression of Apaf-1
Fas antagonist- block T cell cytotoxicity
Autoimmune- increase apoptosis eg. Rheumatoid arthritis
Increase in apoptosis eg. Neurodegenerative
What is apoptosis in oral pathology?
Apoptotic bodies/cells under H&E
Eg. Lichen planus
