mechanism of disease 1 Flashcards
what is cell growth and differentiation
basic mechanisms responsible for turning a zygote into a mature multicellular organism
cell growth = bigger organism more cells
Differentiation = cells become complex and an end to to growth
cell growth precedes differentiation but some overlap
cell growth and differentiation in disease
diseases related to cell growth and diff have 3 groups:
- developmental conditions = related to cell growth or diff or both
e. g. neural tube defects like spina bifida - neoplasia = cancers and tumours
- cardiac hypertrophy
cell growth
two main forms
- hypertrophy = cells get bigger
- hyperplasia = more cells
cell growth is balanced by cell death
hypertrophy
cells become bigger
more proteins, more membranes = cause growth
elevated protein synthesis is big driver of increased cell size
heart is an example
hyperplasia
more cells
caused by cell division and proliferation
- cell cycle important
differentiation
exit from the cell cycle
differentiated cells are post mitotic
a program of cell type-specific gene expression
cell morphology and function changes
anything in common between cell growth and differentiation ?
yes, mechanisms governing them
cell growth and differentiation are governed by integration of multiple signals:
- intra and extracellular signals
signals converge on the promoters of key genes
- promoters act as “ coincidence detectors”
extracellular signals
ligand - receptor = intracellular cascade
three broad classes:
1. 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 = like conventional hormones, 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
- can do either
- induce apoptosis
extracellular signals induce gene expression, how?
- growth factor binds to growth factor receptor
- activate signal transduction pathway via a kinase cascade
- activates transcription factors in nucleus
- TF drive expression of downstream genes incl mRNA
- protein synthesis = proteins made
phases of the cell cycle
mitosis = cell divides into 2 daughter cells
interphase = 3 phases. cell grows in size
S phase = DNA replication
G1 and G2.
diploid > tetraploid after DNA replication
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
fluorescence microscopy
can see cell cycle
Blue = DNA red = gamma tubules green = CHEK2 protein Yellow = centrioles
cell cycle checkpoints
controls and ensures the strict alternation of mitosis and DNA replication
- restriction point: DNA not damaged, cell size, metabolite/nutrient stores
- D2Mphase = DNA completely replicated, DNA not damaged
- chromosomes aligned on spindle
cells responsive to growth factors = main site of control for cell growth
cyclin dependent kinases = CDK
10 genes of CDK proteins
cyclin regulatory subunit = 20 genes
expression induced by growth factors