Cell Death (2)

Growth factors (what they are)

Growth factors are intracellular and extracellular signalling molecules that control the rate of cell growth and division (their presence signals whether to progress through the phases of the cell cycle)

Purpose of checkpoints throughout the cell cycle

Checkpoints ensure that a complete and damage free copy of genome is transferred to daughter cells; each checkpoint can check for errors, if there are errors detected, cell cycle is either aborted or delayed, allowing time for repair

G1 Checkpoint (what it checks for)

G1 checkpoint checks for damaged DNA, sufficient nutrients, and normal cell size and growth patterns

G2 Checkpoint (what it checks for)

G2 checkpoint checks for damaged DNA and error-free DNA replication

Mitosis checkpoint (what it checks for)

Mitosis checkpoint checks for spindle defects in chromosome attachment, correct alignment of chromosomes (to allow for proper separation of chromatids).

How can Mitosis checkpoint result in defects?

Mitosis checkpoint occurs between metaphase and anaphase, however, it is possible for anaphase to occur before the checkpoint, resulting in daughter cells with missing/damaged chromosomes

Why is it important for cells to undergo programmed cell death?

Cells undergo programmed cell death to maintain the balance of cell division and cell death.

What happens when imbalance in cell death exists i. Out of control proliferation

Out of control cell proliferation can result in tumours (mass of cells)

What happens when imbalance in cell death exists ii. Too much cell death

Too much cell death can result in neurodegenerative diseases (excessive apoptosis of neurons)

The two types of cell death

Necrosis and apoptosis

Type of cell death i. Necrosis

Necrosis is cell death caused by serious damage by mechanical or chemical factors. The cell swells and bursts, which leads to inflammation. 'Death signal' comes from outside of cell.

Type of cell death ii. Apoptosis

Apoptosis is programmed cell death. 'Death signal' may be from inside or outside of cell.

Why is apoptosis essential?

Apoptosis is essential for development, shaping organs and tissues, and removing old and unneeded cells.

Apoptosis can be triggered by...

Death signals, withdrawal of survival factors or growth factors, mutations in genes that control the cell cycle

Mechanism of apoptosis (general outline)

Initiation, execution, phagocytosis

Difference between two initiation pathways

Initiation can be triggered by either an internal or external signal, which will either activate the intrinsic pathway, or cause signalling molecules to bind to death receptors and activate the extrinsic pathway.

Intrinsic pathway (detailed details)

The intrinsic pathway is also known as the mitochondrial pathway, as it is dependent on factors released from the mitochondria.

Causes of triggering of internal signal and thus activation of intrinsic pathway

Absence of growth factors, hypoxia, UV, viral infection, DNA damage

Extrinsic pathway (detailed details)

The extrinsic pathway is also known as the death receptor pathway, as it begins when signalling molecules bind to death receptors on the membrane surface.

Causes that trigger an external signal and thus activation of extrinsic pathway

No longer needed old cell, excess number of cells, replaced with new cells, viral infection

General process of extrinsic pathway activation

Signal received at death receptors = activation of caspases = apoptosis

What are caspases?

Enzymes that break down proteins and, when activated, divides other caspases to break down components of the cell

What are macrophages?

Cells that engulf apoptotic bodies

Steps of execution and phagocytosis after initiation stage

Cell shrinks and forms blebs, nucleus degrades and chromatin forms clumps = collapse of nucleus and signalling to attract macrophages = fragmentation of cell; nucleus breaks up into sphere and DNA breaks up = cell breaks up into apoptotic bodies, macrophages remove them via phagocytosis

Factors that indicate necrosis

Cellular swelling, broken membrane, lysis of the cell, random or smeared DNA fragmentation

Factors that indicate apoptosis

Cellular condensation, intact membrane, requires ATP, phagocytosed (no tissue reaction), DNA fragmentation in ladder-like manner