cell growth and cell death Flashcards
which cells go through the cell cycle on a regular basis?
adult stem cells
what are the 3 tissue types grouped based off proliferative activity?
- labile tissues
- stable tissues
- permanent tissues
which tissues are continuously dividing, proliferate throughout life and are derived from stem cells?
labile tissues
- surface epithelia of the skin, columanr epithelium of the GI tract, bone marrow cells, and hematopoietic tissues
which tissues are made of quiescent cells and can divide with appropriate stimulus?
stable tissues
- fibroblasts, endothelial cells, smooth muscle cells, chondrocytes, and osteoblasts
which tissues are made of terminally differentiated cells, unable to undergo division (non-dividing)?
permanent tissues
- neurons, skeletal muscle cells, and cardiac muscle cells
what are the 4 main phases of the cell cycle?
- G1
- S
- G2
- M
what is the 5th phase of the cell cycle?
G0
describe what occurs during G1 growth phase
cell prepares for DNA synthesis and makes proteins needed for DNA replication
describe what occurs during S phase
DNA replication
describe what occurs during G2 growth phase
cell prepares for mitosis; cell grows in size, replicates organelles, etc.
describe what occurs during M phase
mitosis phase consists of telophase, anaphase, metaphase, prophase
describe what occurs during G0 phase
cells no longer divide
- cells exit the cycle in G1 and enter G0
what is temporary G0?
some cells can be placed in G0 temporarily but can be brought back to the cell cycle by external signals; known as quiescence
what is permanent G0?
cells that are differentiated/highly specialized enter a permanent G0 arrest and can never divide again; known as terminally differentiated
what is the DNA content of the cells at each stage of the cell cycle?
G1: n
S: 2n
G2: 2n
M: 2 new daughter cells created
what are mitogens?
class of growth factors that stimulate cells to grow and dividew
when are cells responsive to mitogens?
only G1 (start of the cell cycle)
what does the presence of mitogens in the cell cycle cause?
drives the cell cycle forward, pushing the cell out of G1 into the cell cycle
what does the absence of mitogenic growth factors cause?
cells are pushed from G1 to G0 (quiescence)
list some examples of mitogens
- platelet derived growth factor (PDGF)
- insulin growth factor (IGF)
- epidermal growth factor (EGF)
what role do mitogens play in signaling pathways?
mitogens bind to growth factor receptors which trigger a biological response in the cell to drive the cell cycle forward out of G1
what are the 2 classes of proteins that mediate progression through the cell cycle?
- cyclins
- cyclin dependent kinases (CDKs)
what happens when cyclins and CDKs when they are both present in the cell?
they move from inactive (on their own) to forming an active enzyme complex
what does the active enzyme complex do?
activate target proteins by phosphorylation
what is the first cyclin synthesized in response to mitogen activation?
cyclin D
describe the summary of mitogen activation of cyclin/CDKs
- mitogen interacts with the receptor
- synthesis of cyclin D is stimulated
- cyclin D complexes with CDK4/CDK6
- active cyclin D/CDK4/CDK6 enzyme complex is formed
- enzyme complex causes activation of target proteins
what are 2 important checkpoints of the cell cycle?
- G1 damage checkpoint (mediated by p53 protein)
- G1 restriction checkpoint (mediated by pRb protein)
describe the DNA damage checkpoint
- DNA damage/mutation is recognized by the cell through a series of ‘sensor’ proteins
- sensor proteins trigger the activation of p53 protein
- activated p53 protein triggers either a cell cycle arrest (allowing DNA repair) or cell death
what is the purpose of triggering the DNA damage checkpoint pathway?
the cells containing mutated/damaged DNA are not replicated
what happens if mutations are passed on to daughter cells?
it can lead to genomic instability which can lead to cancer
what is the function of p53 protein?
- tumor suppressor
- protects the cell from the potential harmful events of DNA damage and tumor formation
describe cellular senescence
an intrinsically programmed limit to cell proliferation (most cells have this)
describe replicative or cellular senescence
after a period of cell division, most somatic cells will undergo a permanent growth arrest (limited replicative potential)
describe how senescence differs from G0
senescence cannot be reversed by growth factor stimulation, however senescent cells remain metabolically active
describe what the hayflick limit is and the phases of cell growth in a lab
the limit to cell growth
- phase 1: cells grow rapidly
- phase 2: cell growth is exponential
- phase 3: cells stop growing and can never again enter the cell cycle, cells are said to be senescent
what is a telomere?
specialized DNA structure that is an important regulator of senescence
what is the structure of a telomere?
- complexes of DNA and protein that ‘cap’ linear chromosomes
- noncoding DNA sequence made up of multiple repeats of the sequence TTAGGG
- most of the telomere is double stranded, but the ends are single stranded
what happens to chromosomes if the telomeres are removed?
chromosomes can stick together
what happens to telomeres as they go through cell division?
- telomeres become shortened
- loss of telomere DNA continues with each round of division until telomeres are very short
- this triggers the cell to stop dividing and enter senescence
why do telomeres shorten?
because of the end replication problem in DNA replication
- one strand replicates to the end
- the other strand has a small gap at the 5’ end
- the gap arises with each round of cell division which causes the telomere to get progressively shorter
describe how telomeres trigger senescence
telomeres shorten with increased cell division until the cell stops dividing and enters senescence
what happens when cells maintain their telomere lengths and what are they called?
the signal to enter senescence is bypassed and the cells can divide indefinitely
- immortal cells (this can include cancer cells, stem cells, germ cells)
how is immortality in cells achieved?
expression of telomerase, an enzyme that can synthesize telomere DNA back onto the end of the chromosome
- while the end replication loses DNA, telomerase resynthesizes telomere DNA
list the 3 main cell death pathways
- apoptosis
- necrosis
- autophagy
what is the function of apoptosis?
- homeostasis
- animal development
- cell defense mechanism
give an example of how apoptosis functions in homeostasis
shedding of the uterus lining during menstruation
give an example of how apoptosis functions in animal development
- formation of fingers and toes in the fetus during embryonic development
- resorption of the tadpole tail
- involution (shrinkage) of the mammary gland after weaning
give an example of how apoptosis functions as a cell defense mechanism
- kills cells infected with viruses; if this fails, it can lead to a viral infection
- kills cells carrying DNA mutations
- destroys self reactive lymphocytes; if this fails, it can lead to an autoimmune disease
describe when apoptosis is triggered in the cell
when the cells receive more death signals than survival signals
list some of the pro-apoptotic death signals
- DNA damage (UV or gamma irradiation, chemotherapy)
- growth factor withdrawal (mitogens)
- hypoxia (lack of oxygen)
- ischemia (reduced blood flow)
list the morphological changes that occur in apoptotic cells
- chromatin condenses; DNA fragments resulting in regular size fragments of DNA produced
- cytoplasm shrinks and membrane ‘blebs’ (protrusions that form on the plasma membrane)
- cell contents packaged into membrane bound apoptotic bodies
- phospholipid, phosphatidyl serine, is exposed on the surface (moves from the inside to the outside of the cell)
- receptors on phagocytic cells (macrophages) recognize exposed phospholipid and engulf the cell fragments
what are caspases?
class of enzymes important in apoptosis and activate nucleases (to cleave DNA) and proteases (to cleave proteins) and bring about the morphological changes in apoptotic cells
describe necrosis in the cell
disordered cell death
- form of pathological insult
name the factors that can result in necrosis
- oxygen deprivation
- physical agents (mechanical trauma, extreme heat, electric shock, radiation)
- chemical agents/drugs
- viral/bacterial infections
list the morphological changes that occur in necrotic cells
- chromatin clumps together
- organelles and cell swell
- plasma membrane ruptures
- cell undergoes lysis and disintegrates
- cell contents are spilled out in the surrounding cells and extracellular space
- immune response - inflammation
list the differences between apoptosis and necrosis
apoptosis (programmed cell death):
- cell shrinkage
- nucleus: fragmentation (nucleosome size)
- plasma membrane: budding and altered structure (especially orientation of lipids)
- cellular contents: intact (released in the apoptotic bodies)
- no adjacent inflammation
- removal: phagocytosis by macrophages
- enzymes: caspases activated; DNA fragmentation
necrosis (uncontrolled cell death):
- cell is enlarged
- nucleus: pyknosis (shrunken); karyorrhexis (loss of nuclear membrane)
- plasma membrane: disrupted (rupture and fragmentation)
- cellular contents: enzymatic digestion (may leak out of cell)
- frequent adjacent inflammation
- removal: phagocytosis by macrophages
- enzymes: no caspase activity involved; no DNAse activity (DNA clumps)
