Cell survival and uncontrolled growth Wk 4 Flashcards
What are the hormonal pathways of the hypothalamus, pituitary and liver controlling animal growth in development?
Hypothalamus produces GHRH which acts on the pituitary to release GH which acts on the liver which releases IGF-1 which stimulates growth and survival of tissue cells (muscle, bone & fat).
What role does nutrition and amino acids play in cell growth?
Nutrition controls cell growth, amino acids activate mTORC1.
Where is phosphatidylserine usually? When and why does it move?
On the inside of the phosphoid lipid bylayer; It moves to signal phagocytosis of apoptotic cells during apoptosis.
What is mammary gland regression? When does it happen and how is it controlled?
After peak lactation (mammogenesis), mammary gland cells which have proliferated during pregnancy, undergo controlled apoptosis (involution).
Controlled by BOVINE GROWTH HOROMONE (somatostatin) which inhibits involution.
Why does GHD dwarfism not exist today?
Children are injected with GH in childhood as GHD is understood (whereas it wasn’t when the Wizard of Oz was made re. Munchkin Town and Karl Slover - I’ve put this in for you, Chrissy).
What controls the size of an individual animals?
Hormones.
What controls the size of an individual animals?
Hormones (GHRH, GH & IGF-1).
Why are tiny dogs so small?
Mutations in IGF-1 (proportionate growth).
How does IGF-1 function as a growth signal for cells?
- Binds to IGF-1 receptors at surface of cell.
- Triggers confrontational change, activating the receptor
- Akt protein is activated
- Akt activates mTORC1 (major controller of cell growth).
What cells are post-miotic, what does it mean?
Neuron. Never divide again.
What cells are post-miotic, what does it mean?
Neuron. Muscles. Heart.
Never divide again.
What cells are quiescent cells? Where?
Resting (G0) such as Liver.
Can re-enter cell cycle by circulation factor mitogen, putting them back into cell cycle to proliferate again.
What are circulating cell survival factors?
Factors promoting continued life of the cell.
What are circulating cell death factors?
Factors promoting death of the cell.
What effects the size of a cell?
Growth Factor
What is increased cell size called?
hypertrophy
What is decrease cell size called?
hyperplasia
What does the activation of mTORC1 do?
Cell starts producing the raw materials required for growth.
Other than hormonal control, what else leads to growth?
Mechanical loading (exercise) also causes activation of mTORC1.
What is an example of equine hypertrophy?
Over training and over loading can lead to hypertrophy of the left ventricle heart wall in race horses.
What does the hormone myostatin do?
Binds to myostatin receptors on muscle cells stopping the IGF-1 pathway by inhibiting Akt and mTORC1.
Why do belgian blue and piedmontese cattle have double muscle?
Mutation to myostatin gene; less myostatin produced thus more muscle growth.
Why do belgian blue and piedmontese cattle have double muscle?
Mutation to myostatin gene; less myostatin produced thus more muscle growth. Cells are larger, rather than double the amount of cells.
What two things does cell growth require?
Amino acids and growth factor hormones
What does reduced admino acid in development lead to?
Reduced body size.
What two things does full potential of cell growth require?
Amino acids and growth factor hormones
What does reduced admino acid in development lead to? What’s the classic experiment proving this?
Reduced body size (classic fruit fly experiment).
How does maternal nutrition affect body size of child?
Mother’s childhood nutrition leads to inherited epigenetic changes for one or two generations.
What is apoptosis?
Regulated cell death
During development some cells must die to sculpt tissues and organs; give an example
webbing of digits, tadpole tail, retina blood vessels after birth for efficiency
When does apoptosis occur in adults?
Cancer and faulty cells
What happens to apoptotic cells?
Removed by phagocytosis
What is the first stage of apoptosis?
Proteases called capases digest key protein contents of cell, triggering key changes
What happens to the nucleus during apoptocis?
Fragmented into apoptotic bodies containing DNA
What happens to the plasma membrane?
The plasma membrane forms blebs containing DNA fragments.
How do blebs signal to phagocytes?
Plasma membrane flips the lipid phosphatidyslerine to the outside, signalling “eat me” to phagocytes.
What does phagocytosis of apoptotic fragments prevent?
Inflammation: fibrosis and scaring of the tissue
Autoimmune reactions: developing antibodies against DNA
What is involution and mammogensis?
Expansion and regression of the mammary gland.
What hormone is given to cows to increase milk yield? How does it work?
Bovine growth hormone. Inhibits apoptosis of mammary glands and regression.
How does uncontrolled proliferation occur? What can protect against this?
Mutation to DNA, apoptosis.
What is Hayflick’s number?
The number of times an animal cell can replicate.
What does uncontrolled cell proliferation trigger?
Apoptosis.
What is senescence?
Once a cell reaches Hayflick number it stops proliferating.
How does the body control cancer cells that loose control of proliferation??
Apoptosis and senescence.