Apoptosis and quiescence lectures Flashcards
Apoptosis define
Eliminates cells with DNA damage that fail to be repaired at G1/S or G2/M
Crucial to cell number and morphogenesis
eg. eliminates self-lymphocytes
What morphology of apoptosis can be observed under a microscope?
Cell shrinkage, nuclear condensation/fragmentation, chromosome condensation, releasing apoptotic bodies containing organelles, blebbing(bulges)
How do macrophages recognise apoptotic cells?
Phoshatidylserine exposure (which is usually in cytoplasmic portion of PM)
What did C Elegans studies reveal?
Pro- (BAX, BAK) and anti- (BCL2 and BCL-XL)apoptotic factors, executioner factors (proteolytic enzymes) which cause cascade of digestion destroying cellular contents
What ultimately triggers a proteolytic cascade?
Mitochondria
What is apoptosis triggered in response to?
DNA damage, loss of growth factor signalling, loss of contact with basement membrane, ER stress(accumulation of unfolded proteins in ER lumen)
Draw diagram of BAX and BAK causing apoptosis
See notes for diagram
What receptor family are important in triggering apoptosis?
Death domain
What do death domain receptors bind?
TNF alpha (produced by macrophages) or FasL (on surface of cytotoxic lymphocytes produced in immune response)
What is quiescence?
Cells exit cell cycle, used by memory lymphocytes to preserve pathogen memory
In quiescence:
Cells lower metabolic energy, exit cell cycle, reduce ribosome biogenesis and protein production
Wait until external signal for active cycling
Minimal damage from ROS and low chance of mutation
What is a cell niche?
Allows necessary cell-cell and cell-matrix interactions, could promote quiescence eg. CDK inhibitors preventing G1 entry
Where are epidermal stem cells?
Deepest most basal layer of skin (hypodermis), protected by melanin
Epidermal stem cells…
Regularly regenerate the entire skin, are quiescent but can be activated at any point
What is the point of a 3’ UTR?
Allows low translational activity in quiescence, miRNAs bind and prevent translation of mRNA with 3’ UTR (NB mRNA is normally translated 5’ to 3’)
Draw stem cell diagram
See notes for diagram
How are quiescent cells poised to reenter the cell cycle?
They have loose DNA and histones allowing TF access, histones have post-translational modifications typical of active transcriptional state
RNA pol kept paused due to binding by negative regulators preventing transcription
What happens upon cell activation?
RNA pol is released, there is no need to reset transcriptional programme, cell is good to go
What is fancy name for increase in cell size?
Hyperplasia
Increase in cell no=?
Hypertrophy
What is the growth law in bacteria?
Larger cells proliferate faster and thus maintain cell size uniform under steady state
When is uniform cell size lost in multicellular organisms?
In injury and cancer
What happens to WAC
They expand in number in late embryonic life to a stable number, so adipose tissue grows by accumulation of lipid particles due to diet and no increase in number (hypertrophy)
What factor regulates adipocyte development and height?
Insulin growth factor 1
Participates in cartilage hypertrophy during bone formation of growing limb bones in adolescents
What does research show about amount eaten as child and liklihood of being obese?
The more you eat as a baby the more likely you are to be obese because no. adipose cells set v early, cells store more fat if you eat more as a child
In pregant women beta cells…
Increase in size not number to meet higher blood glucose demands, to make more insulin, as increasing in size is less risky for mistake/cancer than increasing in number
