Cell Death and Damage Flashcards
What are the different causes and mechanism for cell death/damage?
genetic - abnormal chromosomes traumatic damage - direct rupture of cells inflammation infection - intracellular replication physical - heat, cold chemical - acids/corrosives
What is the difference between apoptosis and necrosis?
necrosis
- most common cause of cell death
- occurs after stresses = trauma, chemical injury
- cell death is an accident
apoptosis
- programmed cell death
- designed to eliminate unwanted or unnecessary host cells
- occurs via activation of a co-ordinated, internally programmed series of events effected by a dedicated set of gene products.1
What is the cause of necrosis? What is the function of necrosis?
usually caused by a lack of blood supply to cells or tissues
- injury, infection, cancer, infarction, inflammation
function is to remove damaged cells from an organism
What are the steps involved in necrosis?
whole group of cells is affected
result of an injurious agent or event
reversible events proceed and become irreversible
- makes irreversible changes
energy deprivation causes changes
- lack of oxygen means cells cannot generate ATP
cells swell due to the influx of water
- initial failing proteins are those that regulate balance of electrolytes between the extracellular and intracellular medium = requires ATP for pumps to work
- process is still reversible at this stage, if oxygen is provided it can be reversed
destruction of organelles and nuclear material by
enzymes from ruptured lysosomes
cellular debris stimulates an inflammatory cell response
What are the nuclear changes in a cell due to necrosis?
nuclear changes
- chromatin condensation/shrinkage = from long, thin strands to short and compact
- fragmentation of nucleus
- dissolution of the chromatin by DNase causing fading n the staining of chromatin = random hydrolytic cleavage of the phosphodiester bonds in DNA
What are the cytoplasmic and biochemical changes in a cell due to necrosis?
cytoplasmic changes
- opacification = denaturation of proteins and their aggregation causes the cytoplasm to become opaque (block light)
- complete digestion of cells by enzymes
biochemical changes
- release of enzymes = creatine kinase or lactate dehydrogenase
- release of proteins = myoglobin
What are the steps involved in apoptosis?
single or a few cells are selected
programmed cell death = co-ordinated
irreversible once initiated
events are energy driven
- actively use ATP to kill themselves
cells shrink as the cytoskeleton is disassembled
orderly packaging of organelles and nuclear fragments in membrane bound vesicles
- engulfment = no release of proteases or lipases
new molecules expressed on vesicle membranes stimulate phagocytosis
- no inflammatory response because there is no release of proteases or lipase, are packaged in vesicles
What are the nuclear changes in a cell due to apoptosis?
nuclear changes
nuclear chromatin condenses on nuclear membrane
- chromatin condensation/shrinkage = from long, thin strands to short and compact
DNA cleavage
- cleaved at specific sites
What are the cytoplasmic changes in a cell due to apoptosis?
cytoplasmic changes
- shrinkage of the cell. organelles and nuclear fragments are packed into membrane vesicles
- cell fragmentation. membrane bound vesicles bud off
- phagocytosis of cell fragments by macrophage and adjacent cell
- no leakage of cytoplasmic components
What are the biochemical changes in a cell due to apoptosis?
biochemical changes
- expression of charged sugar molecules on outer and inner surface of membranes (recognised by macrophage and enhances phagocytosis) = no inflammation
- protein cleavage by proteases and caspases
What are the morphological difference between apoptotic and necrotic cells? What is the difference between the DNA fragmentations of apoptotic and necrotic cells?
apoptotic
- cell nucleus has condensed chromatin = appears darker
- cell begins to shrink = appears smaller than normal cells
- DNA fragmentation has the characteristic ladder = nucleosome is intact
necrotic
- cell nucleus swells
- cell swells
- DNA fragmentation looks like a smear = nucleosomes are disrupted and broken down
What is the function of apoptosis?
is a selective process that eliminates unwanted, unnecessary, infected or transformed cells
- infected = by viruses or bacteria
- transformed = cells on the verge of becoming cancerous
What are examples of apoptotic processes?
apoptotic processes
embryogenesis = development of the body (stop webbed hands and feet)
- induced by growth factor deprivation - nerve growth factor
DNA damage-mediated apoptosis
- p53 accumulates when DNA is damaged and arrests the cell cycle enabling the cell to repair the damage
- if the repair process fails, p53 triggers apoptosis.
metamorphosis = animal development
endocrine dependent tissue atrophy = reduce in size (breast cells after breastfeeding)
What are the two types of apoptosis?
intrinsic = within the cell
- DNA damage
- interruption of the cell cycle
- inhibition of protein synthesis
- viral infection
- change in the redox state
extrinsic = outside the cell
- withdrawal of growth factors
- extracellular signals = TNF (tumour necrosis factor)
What are caspases? How can caspases be activated?
cysteine proteases
- are enzymes that catalyse proteolysis
- play a role in apoptosis inhibition
- apoptosis is mediated by an intracellular proteolytic cascade = inactivation of caspases prevents apoptosis
caspases are activated by proteolysis = are synthesised as their inactive precursors
- proteolysis is initiated by other initiator caspases
proteolysis = breakdown of proteins
