Cell death regulation: trophic factors

-Every cell of our body requires certain signals to stay alive

-these signals are called trophic factors

-trophic factors include for example neutrophins like NGF (nerve growth factor)

-in the absence of trophic factors, cells commit "suicide"

-a cell might also be murdered by killing signals from other cells

-in both cases, suicide and murder, the cell dies through programmed cell

death, often referred to as apoptosis

-apoptosis is mediated by a common molecular pathway

Stimulation of apoptotic mechanisms:

-a number of extrinsic and intrinsic signals stimulate apoptotic mechanisms

-the sensitivity of cells to these stimuli varies, depending on:

-balance of pro- and anti- apoptotic proteins

-severity of stimulus

-stage of cell cycle

-some major stimuli are:

here:

picture of a cell with its compartments and numbers that relate to the

following text

1) binding of death inducing ligands to cell surface receptor

2) cellular stress (radiation, chemicals etc.)

3) viral infection

4) cytotoxic T-lymphocytes

Induction and Inhibition of Apoptosis:

-in the absence of trophic factors, direct interactions between pro-apoptotic

and anti-apoptotic proteins lead to cell death.

-most of the pro- and anti- apoptotic proteins belong to a family of trans-

membrane proteins called Bcl-2

Pro-apoptotic proteins/ Apoptosis promoters:

-the cell is more sensitive to apoptosis, when there is an excess of pro-

apoptotic proteins

-pro-apoptotic proteins of the Bcl-2 familiy are:

-Bad

-Bax

-Bid

-Bik

-Bcl-xS

-Hrk

Anti-apoptotic proteins/ Apoptosis inhibitors

-the cell is less sensitive to apoptosis, when there is an excess of anti-

apoptotic proteins

-anti-apoptotic proteins of the Bcl-2 familiy are:

-Bcl-2

-Hcl-1

-Bcl-xL

-Bcl-w

=> survival or death of a cell is dependent on

1) the particular spectrum of Bcl-2 family members present in the cell

2) the intracellular signaling pathways that regulate them

The apoptotic pathway:

-bcl-2

-caspases (cysteine proteases)

-cytochrome c

.... the pathway will be explained briefly

here: 2 figures that illustrate caspase activation and inhibition of caspase

(source: Molecular cellbiology, 23.8 Cell death and its regulation)