Cell growth, divsion and death Flashcards
How do you calculate tissue growth?
cell # * average cell size
What are the two overall factors that impact cell growth (intrinsic vs. extrinsic)
1) genes, developmentally programmed
2) nutrient availability
What three things determine the cell size and the number of cells?
1) cell death
2) cell growth
3) cell division
What determines cell number?
+ cell division
- cell death
What determines cell size?
cell growth (means increase mass of individual cells)
+ synthesis of molecules/ proteins
- degradation of molecules / proteins
Growth is (a) of division
UPSTREAM
Describe genetic control of cell size based on nutrient availability
LOW NUTRIENTS… there are only a few ribosome per mRNA, therefore ribosome likely won’t jump across from stop codon to cyclin coding sequence…. thus no cyclin/CDK being active = cell cycle arrest
HIGH nutrients… there are a lot of ribosomes per mRNA, therefore more likely ribosome will jump across stop codon and start translation at cyclin coding sequence… this lots of active cyclin/CDK,…. which promotes G1/S transition
Independent molecular mechanisms of cell division and growth
cell growth occurs INDEPENDENTLY of cell division (can occur separately)
T or F: Growth is a consequence of division
FALSE
altering proliferation of cells within a tissue does not change the rate at which a tissue grows (ie. acquires mass/ cytoplasm)
If you reduce the nutrition for a cell, the cell cycle becomes (a)
SLOWER… the cell waits at the G1/S transition for the cell to get big enough to divide
Metcalf’s experiments
transplanted multiple spleens into newborn mice…. grew to FRACTIONAL size = systemic control (nearby organs secrete factors to inhibit growth)
transplanted multiple thymuses into mice… grew to NORMAL size = local control
Myostatin is a systemically acting protein that
controls the muscle mass (ONLY IN SKELETAL MUSCLE CELLS)
Does IGF-1 and Tsc/Tor increase or decrease cell growth?
IGF-1= increase in any cell that expresses IGF-1 receptor (meaning bigger cytoplasm) Tsc/Tor = increase or decrease
What two intrinsic pathways control cell growth?
IGF-1 (developmentally programmed) and Tsc/Tor (nutrient availability, calibrate growth to environment)
Describe how IGF-1 is secreted
hypothalamus releases GHRH–> anterior pituitary –> released GRH or HGH —> liver–> released IGF-1–> muscle, bone, fat cells, etc.
Describe in cell bio detail how IGF-1 increases translation & cell growth (bigger cytoplasm)
IGF-1 binds extracellular receptor –> activates IRS-1 –> activates PI3K (lipid kinase)–> phosphorylates PIP2 turning it to PIP3 –> PIP3 goes to internal leaflet of membrane–> activates PDK1 and AKT—> Both activate S6K (= assembling more ribosomes)
AKT inhibits eIF-4eBP, which is inhibiting eIF-4e….. eIF-4e typically is a TF for initiating translation, so inhibiting the inhibitor = more translation
What is a brake on the IGF-1 pathway?
PTEN (lipid phosphatase) that converts PIP3 back to PIP2
Describe in cell bio detail the Tsc/ Tor pathway
Tsc1/Tsc2—> INHIBIT Rheb (thus decreasing cell growth)
Rheb (GTPase) –> activates Tor (kinase)—> activate S6K (= assembling more ribosomes)
Nutrients from membrane nutrient importer also activate Tor (kinase)
Tor inhibits eIF-4eBP, which is inhibiting eIF-4e….. eIF-4e typically is a TF for initiating translation, so inhibiting the inhibitor = more translation
OVERALL, Tsc decreases cell growth, and Tor increases cell growth
What drug can inhibit Tor?
rapamycin
Necrosis
damage induced cell death (response to injury)
cell swells, release of contents, inflammation
PASSIVE PROCESS
Apoptosis
programmed cell death
cell shrinks, engulfment of apoptotic body –> phagocytosis, NO inflammation, highly regulated (signal transduction)
ACTIVE PROCESS
What enzymes drive apoptosis? and when are they active?
caspases!
constitutively expressed but only active once pro domain is cleaved (so only active in dying cells)… fragment genome, cleave and destroy cellular proteins, cleave and activate other proteins
Describe in cell bio detail how caspases get active
Typically, Bcl2 inhibits pores in mitochondrial membrane and keeps cyt c in there
When there are intrinsic death factors (many signals)–> BH3 is activate –> inhibits BCL2—> creates pores in mitochondrial membrane—> release of cyt c and it binds with apaf-1 in the cytoplasm–> create an apoptosome (wagon wheel of death) –> activates caspase by cleavage of pro-caspase
What are the extrinsic signals that can regulate caspases and cause mass cell death?
pro death ligands (ie. FASL, TRAIL, TNF-alpha)
