Lesson 7 Flashcards
What are five important types of cell adaptation?
- Regeneration
- Hyperplasia
- Hypertrophy
- Atrophy
- Metaplasia
What are the stages in cellular response to stress?
Normal cell
- > adaptation
- > cell injury
- > subcellular
- > reversible cell injury
- > necrosis
Explain differences in size of cell population
• Depends on rate of cell proliferation, cell
differentiation and cell death by apoptosis
• Increased numbers are seen with increased
proliferation/decreased cell death
• Proliferation occurs in physiological + pathological conditions
• Proto-oncogenes regulate normal cell proliferation
What are some chemicals that stimulate cells in multicellular organisms?
Hormones
Local mediators
Direct cell-cell or cell-stroma contact
Cell proliferation is largely controlled by signals (soluble or contact dependent) from the microenvironment which either stimulate or inhibit cell proliferation.
What are intercellular signalling mechanisms in cell growth?
• Autocrine – the same secreting and responding cell
• Paracrine – secreting cell and responding cell are
different, but co-located (same organ, eg gut)
• Endocrine - endocrine organs synthesise hormones- conveyed through blood stream-target organs distant from site of synthesis
What are some final outcomes of signalling biochemistry?
Survive – resist apoptosis
Divide – enter cell cycle
Differentiate – take on specialised form and function
Die – undergo apoptosis
What are key points about apoptosis?
- Programmed cell death
- Physiological
- Cell collapses and disappears
- Internal & external signals
What are key points necrosis?
- Cell death – gross tissue death
- External agents
- Ischaemia
- Toxin
- Trauma
- Infection
- Heat/cold etc
What is the general purpose of growth factors?
- Local mediators involved in cell proliferation
- Coded by proto-oncogenes
- Polypeptides that act on the cell surface
- Local hormones
- Stimulate cell proliferation, may also affect cell locomotion, contractility, differentiation and angiogenesis.
Explain epidermal growth factor (EGF)
–Mitogenic for epithelial cells, hepatocytes and fibroblasts
–Produced by keratinocytes, macrophages and inflammatory cells
– Binds to epidermal growth factor receptor (EGFR)
Explain vascular endothelial growth factor (VEGF)
Potent inducer of blood vessel development (vasculogenesis)
Role in growth of new blood vessels (angiogenesis) in tumours, chronic inflammation and wound healing
Explain platelet-derived growth factor (PDGF)
Stored in platelet alpha granules and released on platelet
activation
Produced by macrophages, endothelial cells, smooth muscle cells and tumour cells
Causes migration + proliferation of fibroblasts, smooth muscle cells and monocytes
Explain granulocyte colony stimulating factors (GCSF)
Treatment to stimulate poorly functioning bone marrow
eg: during chemotherapy & renal failure
What happens when cells are instructed to divide?
Increased growth occurs by:
• Shortening the cell cycle
• Conversion of quiescent cells to proliferating cells by making them enter the cell cycle.
What are the cell cycle stages?
G1 = gap 1, presynthetic, cell grows S = DNA synthesis G2 = gap 2, premitotic, cell prepares to divide M = mitosis
What do the G1 and G2 checkpoints indicate?
G1 - is cell big enough? Is env. favourable? Is DNA damaged?
G2 - is all DNA replicated? Is cell big enough?
Describe Restriction (R) point
- Majority of cells that pass the R point will complete the full cell cycle – point of no return
- R point - most commonly altered checkpoint of cell cycle in cancer cells
- Checkpoint activation delays cell cycle and triggers DNA repair mechanisms or apoptosis via p53
What allows for control of cell cycles? - Cyclins and CDKs
- Progression through cell cycle, particularly G1/S transition, is tightly regulated by proteins (cyclins) + associated enzymes, cyclin-dependent kinases (CDKs). CDKs become active by binding to/complexing with cyclins.
- Activated CDKs drive the cell cycle by phosphorylating proteins that are critical for cell cycle transitions, e.g., retinoblastoma susceptibility protein.
- Many growth factors stimulate production of cyclins.
- Activity of cyclin-CDK complexes is tightly regulated by CDK inhibitors. Some growth factors shut off production of these inhibitors.
Explain how cell population can be classified according to their ability to enter the cell cycle
• Labile:
• (G1 -> S -> G2 -> M) -> (G1 -> S -> G2 -> M) -> etc.
• Stable:
• G0 (+ growth stimulus) -> (G1 -> S -> G2 -> M) for 1 or
more rounds -> G0
• Requires activation of a large number of genes, e.g., proto-oncogenes, genes required for ribosome synthesis and protein translation.
• Permanent:
• G0 -> terminal differentiation
