Chap. 21 Problem 11

Experiments performed with knockout mice indicate that neurons in the brain and other tissues die by apoptosis in animals in which neurotrophins or their receptors are inactivated (Fig. 21.36, skin & muscle). This indicates that apoptosis is the default pathway in the absence of trophic factors.

Chap. 21 Problem 12Apoptosis is a regulated program that can be induced by withdrawal of trophic factors, which signal cells to stay alive, or by receipt of death signals like tumor necrosis factor, which trigger apoptosis. The structural changes that occur during apoptosis are morphologically distinct from changes that occur due to cell death via necrosis (Fig. 21.30). In necrosis, cells typically burst and release their contents outside. This damages surrounding cells and can lead to inflammation. In apoptosis, cells shrink, condense, and fragment without the release of cell contents. Cell fragments known as apoptotic bodies are later phagocytosed. Apoptosis proceeds via the same morphological events regardless of whether it is triggered by a death signal or by withdrawal of a trophic factor. This is because the same intracellular processes are triggered by the two types of signaling.

Chap. 21 Problem 16 a) Bad is a pro-apoptotic

factor that is activated in the absence of trophic factors (Fig. 21.38). Phosphorylation of Bad in the presence of a trophic factor inhibits its pro-apoptotic activity. Thus, a mutation that blocks Bad phosphorylation will cause cells to undergo apoptosis even in the presence of trophic factors.

b & c) Cells that overexpress Bcl-2, an anti-apoptotic factor should not undergo apoptosis even in the absence of trophic factors. Likewise, Bax mutations that block its oligomerization should interfere with apoptosis.

Both b & c types of mutations could contribute to cancerous transformation due to the fact that they block apoptosis even in the absence of trophic factors.