mechanisms of disease I Flashcards
3 groups of disease related cell growth differentiation
developmental conditions = can be related to cell growth or differentiation
neoplasia = cancer and tumours
others = cardiac hypertrophy
two forms of cell growth
hypertrophy = bigger cells
hyperplasia = more cells, most common
- cell growth is balanced by cell death
hypertrophy
- cells growing bigger
- more proteins = more membranes. elevated protein synthesis = big driver of increased cell size
heart is an example
hyperplasia
more cells , caused by cell division or proliferation
differentiation explained
- exiting from the cell cycle
- program of cell type-specific gene expression
- cell morphology and function changes
similarities
cell growth and differentiation governed by integration of multiple signals
- intra and extracellular signals
signals converge on promoters of key genes = promoters act as co-incidence detectors
extracellular signals (recap)
ligand - receptor - intracellular cascade
3 broad classes:
- paracrine = produced locally to stimulate proliferation of diff cell type that has appropriate cell surface receptor
- autocrine = produced by cell that expresses appropriate cell surface receptor
- endocrine = released systemically for distant effects
extracellular signals in cell growth and differentiation
proteins that:
stimulate proliferation and promote survival
- mitogens e.g. growth factors and interleukins
- induce differentiation and inhibit proliferation
- induce apoptosis
face analysis of cell DNA content
if DNA stain is applied, FACs can measure DNA content of every cell in a population
data used to plot a graph
mitosis steps RECAP
- prophase
- nucleus becomes less definite
- micro tubular spindle apparatus assembles
- centrioles migrate to poles
pro metaphase
- nuclear membrane breaks down
- kinetochores attach to spindle in nuclear region
- metaphase
- chromosomes align in equatorial plane - anaphase
- chromatids separate and migrate to opposite poles - telophase
- daughter nuclei form
cytokinesis
- division of cytoplasm
- chromosomes decondense
what do the cell cycle checkpoints do
control (involving specific protein kinases and phosphates) and ensure strict alteration of mitosis and DNA replication
cyclin-dependent kinases
CDK = catalytic subunit, 10 genes
cyclin = regulatory subunit = 20 genes. expression induced by growth factors
active cyclin-CDK complex = phosphorylates specific substrates
regulation of cyclin-CDK activity
- cycles of synthesis and destruction
- post transitional modification by phosphorylation = may result in activation, inhibition or destruction
dephosphorylation
binding of cyclin-dependent kinase inhibitors
retinoblastoma protein
- RB = key substrate of G1 and G1/S cyclin dependent kinases
- unphosphorylated RB binds E2F transcription factor preventing its stimulation of S-phase protein expression
- released E2F stimulates expression of more cyclin E and S-phase proteins e.g. DNA polymerase, thymidine kinase, PCNA etc
describe how DNA damage triggers cell cycle arrest or apoptosis
the DNA completely replicated, not damaged
chromosomes aligned on the spindle
DNA not damaged, cell size, metabolite/nutrient stores
= stop the cycle with CDK inhibitors
attempt DNA repair with nucleotide or base excision enzymes
programmed cell death, if repair is impossible
