Activation of Fas activates caspasc-8, which cleaves the protein Bid (in additio

Question

Activation of Fas activates caspasc-8, which cleaves the protein Bid (in addition to other targets) to produce an active fragment, tBid (truncated Bid) that binds to the mitochondrial membrane. tBid promotes oligomerization of Bax and Bak which stimulates the release of cytochrome c into the cytosol to trigger events leading to apoptosis (see Figure 1). To study this pathway in more detail you have generated mouse embryo fibroblasts (MEFs) that are Bax-/- or Bak-/-, or knockouts for both genes. Bak-/-, Bax-/-. You also construct a vector that expresses tBid so that you can study the process independent of Fas. You also generate another vector that can express Bcl-2. In untreated MEFs and in MEFs treated with the empty vector, very few cells are observed to undergo apoptosis (Figure 2). By contrast, when MEFs arc treated with the vector that expresses tBid, the wild-type cells and the cells individually defective for Bax or Bak show a dramatic increase in apoptotic cells. MEFs that arc defective for both Bak and Bax arc resistant to tBid expression showing no increase in the number of apoptotic cells. Among the various mutant cells, cytochrome c is retained in the mitochondria only in the double-knockout MEFs treated with tBid.

Explanation / Answer

b) Above pathway is intrinsic pathway of apoptosis. In the intrinsic pathway, the release of cytochrome C from mitochondria and its binding to Apaf-1 occurs in the cytosol triggering apoptosis. In extrinsic pathway there is no release of cytochrome c from mitochondria.

Bid protein activates the initiator caspase 8 by its cleavage. After activation only, it can bind to mitochondria.

c) Caspase 8 is regarded as an initiator caspase.It initiates other Caspase executioner proteins (3,6 or 7) during cleavage of the protein Bid. Initiator Caspase is activated on binding to oligomeric binding protein.

d)Caspase 3 is effector or executioner caspase. It becomes inactive when binds to inhibotory protein. So, it will inhibit apoptosis.

e) bcl-2 is anti apoptotic, it inhibits the process of apoptosis. It is present on the mitochondrial membrane hence it is involved in the intrinsic pathway.

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