mechanism of disease 1 Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

what is cell growth and differentiation

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

cell growth and differentiation in disease

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

cell growth

A

two main forms

  1. hypertrophy = cells get bigger
  2. hyperplasia = more cells

cell growth is balanced by cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

hypertrophy

A

cells become bigger

more proteins, more membranes = cause growth

elevated protein synthesis is big driver of increased cell size

heart is an example

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

hyperplasia

A

more cells
caused by cell division and proliferation

  • cell cycle important
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

differentiation

A

exit from the cell cycle

differentiated cells are post mitotic

a program of cell type-specific gene expression

cell morphology and function changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

anything in common between cell growth and differentiation ?

A

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”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

extracellular signals

A

ligand - receptor = intracellular cascade

three broad classes:
1. paracrine = produced locally to stimulate proliferation of diff cell type that has appropriate cell surface receptor

  1. autocrine = produced by cell that expresses appropriate cell surface receptor
  2. endocrine = like conventional hormones, released systemically for distant effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

extracellular signals in cell growth and differentiation

A

proteins that:

  • stimulate proliferation and promote survival
  • mitogens
    e. g. growth factors and interleukins
  • induce differentiation and inhibit proliferation
  • can do either
  • induce apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

extracellular signals induce gene expression, how?

A
  1. growth factor binds to growth factor receptor
  2. activate signal transduction pathway via a kinase cascade
  3. activates transcription factors in nucleus
  4. TF drive expression of downstream genes incl mRNA
  5. protein synthesis = proteins made
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

phases of the cell cycle

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

face analysis of cell DNA content

A

if DNA stain is applied, FACS can measure DNA content of every cell in a population

data used to plot a graph

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

fluorescence microscopy

A

can see cell cycle

Blue = DNA 
red = gamma tubules 
green = CHEK2 protein 
Yellow = centrioles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

cell cycle checkpoints

A

controls and ensures the strict alternation of mitosis and DNA replication

  1. restriction point: DNA not damaged, cell size, metabolite/nutrient stores
  2. D2Mphase = DNA completely replicated, DNA not damaged
  3. chromosomes aligned on spindle

cells responsive to growth factors = main site of control for cell growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

cyclin dependent kinases = CDK

A

10 genes of CDK proteins

cyclin regulatory subunit = 20 genes
expression induced by growth factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

regulation of cyclin-CDK activity

A

cycles of synthesis and destruction

post translational modification by phosphorylation
- may result in activation, inhibition or destruction

dephosphorylation
binding of CDK inhibitors, bind to complexes

17
Q

retinoblastoma protein

A

a substrate of G1 and G1/S cyclin dependent kinases

binds to E2F transcription factor = prevents E2F from binding to promoter genes and promoting transcription

if cyclin D-CK4 AND E-CDK2 = dissociation

released E2F = stimulates expression of more cyclin E and Phase proteins e.g. DNA polymerase, thymidine kinase and DNA replication starts

18
Q

sequence of events triggered by growth factors

A
  1. growth factor signalling activates early gene expression (FOS, JUN, MYC)
  2. early gene products stimulate delayed gene expression (incl cyclin D, CDK2/4, E2F TF)
  3. E2F sequestered by binding to unphosphorylated retinoblastoma protein (RBC)
  4. G1 cyclin-CDK complexes hypophosphorylate RB and G1/S cyclin-CDK complexes hyperphosphorylate RB releasing E2F
  5. E2F stimulates expression of more cyclin E and S-phase proteins
  6. S phase cyclin CDK and G2/M cyclin-CDK complexes build up in inactive forms. these switches are activated by post-translational modification or removal of inhibitors, driving cell through S phase and mitosis
19
Q

what if there is DNA damage

A

triggers cell cycle arrest or apoptosis

  1. stop the cycle by CDK inhibitors
  2. attempt to DNA repair = by nucleotides or base excision enzymes, mismatch repair etc

if repair is impossible = programmed cell death

20
Q

role of TP53

A

aka p53

destroyed by proteasome

in response to DNA damage, kinase activation. occurs
phosphorylate p53 = no longer be destroyed

can be accumulated

can:

  • drive expression of CDK inhibitors
  • activation of DNA repair
  • repair not possible = apoptosis
21
Q

TP53 and cancer

A

tp53 loss of function mutations are amongst the most frequent in cancer

  • prevent cell cycle arrest
  • prevent apoptosis
  • prevent DNA repair
22
Q

chemotherapy

A

traditional chemotherapeutic drugs act on cell cycle
- stop proliferation, induce apoptosis

s phase drugs cause DNA damage

  • 5-fluorouracil = prevent synthesis of thymidine
  • cisplatin = binds to DNA causing damage and blocking repair

M-phase drugs target mitotic spindle
- vinca alkaloids = stabilise free tubules and prevent microtubule polymerisation and arrest cells in mitosis

  • paclitaxel = taxol
  • stabilise microtubules and prevent de-polymerization
    arrest cells in mitosis

not just cancer: colchicine is used for immune suppression