Cellular death Flashcards
What happens when a gene is active and follow the process on from there?
RNA is transcribed. The mRNA then exits the nucleus to be translated on cytoplasmic ribosome. This forms proteins for structure and function.
Can you give an overview of how a protein is made and the name the processes that occur?
Transcription then translation
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Can genetic disorders be inheritable?
Yes, this is known as germ line. Genetic disorders that are not inheritable are known as somatic.
What are the three main ways that single gene disorders can occur?
- Missense mutation- When there is a different nucleotide produced resulting in a different protein.
- Silent mutation- Different nucleotide produced however coding for the same protein that was going to be produced
- Nonsense mutation- Different nucleotide producing a stop codon.
What is a frameshift mutation?
Where there is an addition or deletion of a number of bases that would result in a frame shift, which can result in different frame sequence downstream from the amino acid.
What can single gene disorders result in and the main one?
1. Enzyme defects
- Membrane R and transport systems
- Structure, function or quality of non-enzymes
- Unusual drug reactions
How does enzyme defects occur in single gene disorders?
- Accumulation of substrate and or/intermediate substrates that may be toxic in high concentration (lysosomal storage disease)
- Metabolic block (glycogen storage diseases)
- Failure to inactivate damaging substrates (anti-trypsin deficiency).
What other types of disorders can occur other than gene?
Chromosomal disorders and single gene disorders of the germ line.
- Chromosomal most often errors in cell division. (Downs)
- Germ lines- X linked, autosomal dominant, Huntingdons disease etc. Turners syndrome in mares, X monosomy, small uterus and fail to cycle as a result.
What is cellular ageing?
Cellular ageing is the result of a progressive decline in cellular function and viability caused by genetic abnormalities and the accumulation of cellular and molecular damage due to the effects of exposure to exogenous influences.
Can you show cellular ageing in a diagram?
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How can cell death occur?
Necrosis: A degradative reaction occurring after the death of a cell.
Apoptosis: A gene-directed programme of cell death- can be manipulated.
Can you show some features that illustrate necrosis in a cell?
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What are the two main changes in necrosis?
Cytoplasmic change and nuclear change
How does H and E show this and why?
- Eosin is negative and the protein tissues, collagen, and mitchondria are positive resulting in a more eosinophilic response.
- Haematoxylin is positive and the nucleic acids (DNA & RNA) are negative resulting in a more haematoxylin response when nuclear change occurs.
What are the features of nuclear change and what do they mean?
Pyknosis- shrinking of the nucleus to a more concentric form.
Karyorrhexis- fragmenting of the nucleus.
Karyolysis- Complete dissolution of the chromatin from the nucleus.
Can you show the apoptotic process?
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What is happening in this picture?https://s3.amazonaws.com/brainscape-prod/system/cm/173/274/937/q_image_thumb.png?1450536740
Phagocytosis of the apoptotic fragments (also known as secondary necrosis)
What is happening in this picture? https://s3.amazonaws.com/brainscape-prod/system/cm/173/274/999/q_image_thumb.png?1450536942
This is known as a sunburn cell and is an indicator of apoptosis in the EPIDERMIS
Name the 4 ways which activate caspases- which in turn cause apoptosis?
- Cell stress (DNA damage/p53 upregulation)
- Fas/TNFR
- Lack of growth factors, unphosphorylated bad
- Perforin/granzyme B
What are caspases and what are the two classes?
Caspases present as zymogens within healthy cells. When activated by enzymatic removal of prodomain, they can cleave carboxyl side of aspartic acid (D) residues.
- Intiator caspase- long prodomains allowing them to bind to adaptor molecules
- Executioner caspases have short prodomains and cleave death substrates at aspartic acid (D)
What happens once a caspase is activated, what signals the cell to die?
Death inducing signalling complexes (DISCs)
-FasL+Fas+FADD+procaspase 8
(extrinisic pathway)
-Cyt.c+Apaf-1+procaspase-9+dATP
(intrinsic pathway)
Can you explain the intrinsic pathway of DISCs?
Starts inside the cell
Anti apoptotic proteins like bel-2 reduce the permeability of cytochrome c to be released in the mitochondria. Bad however reduced bel 2 and increase the permeability and with it the release of cyt-c. Caspase recruitment of Apaf-1 and card then bind to cyt c and are activated. Recruit other caspases and keeps recruitment until activation (oligomerisation). This process activates the executioner caspases to come and cleave death substrates.
Can you explain the extrinisic pathway of DISCs?
Starts outside the cell
Procaspses in close proximity activate each other (Oligomerisation) which activate intiator caspases. Fas also known as CD95 activates the Fas receptor. Causing the FADD to activate the death domain and the intiator caspase (procaspase 8) to activate the executioner and these cleave death substrates (granenzymes/lysozymes).
What else is programmed cell death thought to now include?
Nercroptosis (RIPK3-dependent)
- implicated in IBD, infaraction
- affects membrane channels
Pyroptosis (inflammasome formation)
- inflammasome formation
- inflammation and killing of pathogens
- proinflammatory response
When does apoptosis occur?
- In developmental growth
- normal wear and tear of tissues
- resolution of inflammation
- response to irradiation and cytotoxic drugs
- dieases eg. neurodegenerative diseases
How do you measure apoptosis? What test
TUNEL assay which stands for terminal deoxynucletidyl transferase (Tdt) Uridine Nick End labelling.
What are the other tests to measure specific proteins? (in dark light)
Flow cytometry- (immunofluorescence)
Antibodies recognise specific moleucles in the surface of some cells. The antibodies are artificially conjugated to fluorochromes. The fluorescence intensity is then measured. The detection of sub G1 Dna content then can be a strong indicator of those cells that have not undergone mitosis.
