Lesson 7

Question 1

What are five important types of cell adaptation?

Answer 1

1. Regeneration
2. Hyperplasia
3. Hypertrophy
4. Atrophy
5. Metaplasia

Question 2

What are the stages in cellular response to stress?

Answer 2

Normal cell

• > adaptation
• > cell injury
  • > subcellular
  • > reversible cell injury
    • > necrosis
    -> apoptosis (related to cell injury)

Question 3

Explain differences in size of cell population

Answer 3

• 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

Question 4

What are some chemicals that stimulate cells in multicellular organisms?

Answer 4

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.

Question 5

What are intercellular signalling mechanisms in cell growth?

Answer 5

• 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

Question 6

What are some final outcomes of signalling biochemistry?

Answer 6

Survive – resist apoptosis
Divide – enter cell cycle
Differentiate – take on specialised form and function
Die – undergo apoptosis

Question 7

What are key points about apoptosis?

Answer 7

• Programmed cell death
• Physiological
• Cell collapses and disappears
• Internal & external signals

Question 8

What are key points necrosis?

Answer 8

• Cell death – gross tissue death
• External agents
  
  • Ischaemia
  • Toxin
  • Trauma
  • Infection
  • Heat/cold etc

Question 9

What is the general purpose of growth factors?

Answer 9

• 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.

Question 10

Explain epidermal growth factor (EGF)

Answer 10

–Mitogenic for epithelial cells, hepatocytes and fibroblasts
–Produced by keratinocytes, macrophages and inflammatory cells
– Binds to epidermal growth factor receptor (EGFR)

Question 11

Explain vascular endothelial growth factor (VEGF)

Answer 11

Potent inducer of blood vessel development (vasculogenesis)

Role in growth of new blood vessels (angiogenesis) in tumours, chronic inflammation and wound healing

Question 12

Explain platelet-derived growth factor (PDGF)

Answer 12

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

Question 13

Explain granulocyte colony stimulating factors (GCSF)

Answer 13

Treatment to stimulate poorly functioning bone marrow

eg: during chemotherapy & renal failure

Question 14

What happens when cells are instructed to divide?

Answer 14

Increased growth occurs by:
• Shortening the cell cycle
• Conversion of quiescent cells to proliferating cells by making them enter the cell cycle.

Question 15

What are the cell cycle stages?

Answer 15

G1 = gap 1, presynthetic, cell grows
S = DNA synthesis
G2 = gap 2, premitotic, cell prepares to divide
M = mitosis

Question 16

What do the G1 and G2 checkpoints indicate?

Answer 16

G1 - is cell big enough? Is env. favourable? Is DNA damaged?

G2 - is all DNA replicated? Is cell big enough?

Question 17

Describe Restriction (R) point

Answer 17

• 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

Question 18

What allows for control of cell cycles? - Cyclins and CDKs

Answer 18

• 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.

Question 19

Explain how cell population can be classified according to their ability to enter the cell cycle

Answer 19

• 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