Apoptosis

Question 1

Pyknosis

Answer 1

chromatin undergoes condensation forming patches against the nuclear envelope - In apoptosis

Question 2

karyorrhexis

Answer 2

Nuclear envelope becomes discontinuous and the DNA is fragmented (in apoptosis)

Question 3

Bcl

Answer 3

B-Cell Lymphomas

Inhibits apoptosis by blocking release of Cytochrome C from mitochondria.

Question 4

Bak/Bax

Answer 4

Assists in Initiating apoptosis by forming a pore in mitochondria allowing cytochrome C release. (Intrinsic Pathway)

Question 5

Apaf-1

Answer 5

Apoptotic protease-activating factor 1

Binds cytochrome C forming wheel of death to activate caspases.

Question 6

Intrinsic Pathway

Answer 6

Bax or Bak inserts into mitochondrial membrane and releases Cytochrome C.

Cytochrome C binds Apaf-1 then procaspases (wheel of death)

Procaspases cleaved to active caspases (9) .

Question 7

Extrinsic Pathway

Answer 7

Initiated by Tumor Necrosis Factor (TNF) receptor family such as the Fas receptor.

Killer lymphocytes bind Fas death receptors which recruits FADD

Procaspases aggregate at FADD site creating the Death Inducing Signaling Complex (DISK)

Procaspases cleaved to active caspases (8 & 10)

Question 8

FADD

Answer 8

Fas Associated Death Domains (Extrinsic pathway)

Cause procaspase aggregation and formation of DISK that cleave to caspases.

Question 9

Perforin/Granzyme Pathway

Answer 9

In response to Viral infected cells

Cytotoxic T-Cells secrete Perforin & Granzymes

Perforin created a pore for granzymes (proteases) to enter the cell

Granzymes activate caspases 8 & 10 that destroy inhibitors of apoptosis AND activates caspase 3 that initiates apoptosis

Question 10

Bid

Answer 10

Pathway linker

Protein activated by caspase 8 in the extrinsic pathway that will block Bcl and activate Bax and Bak in the Intrinsic pathway

Question 11

Survival Factors

Answer 11

Extracellular signals that activate Bcl thereby blocking Bax/Bak (intrinsic pathway) and Bad (a proapoptotic protein

Question 12

p53 in apoptosis

Answer 12

-Cellular and DNA damage results in the activation of p53 via protein kinase -P that causes the transcription of Bax (intrinsic pathway) p21 (cell cycle inhibitor) and Fas receptors (extrinsic pathway)

Question 13

Apoptosis Markers

Answer 13

1) DNA fragmentation can be detected in cells in situ by using DNA end labeling such as TUNEL(Terminal transferased UTPNick End Labeling)
2) Annexin 5 binds to phosphatidyl serine and is usually present on the inner membrane surface of the cell. In apoptotic cells it is present on the outer surface. Labeled antibodies for Annexin 5 can label apoptotic cells
3) Enzymatic assays can be used to detect active caspase

Question 14

Role of Apoptosis in Cancer

Answer 14

1. Apoptosis eliminates damaged cells, especially those possessing DNA damage that can result in cancer.
2. Tumor suppressor p53 controls the apoptotic response to damage.
3. Most cancer cells are defective in apoptotic response and as a result damaged and mutant cells survive.
4. Cancer cells express high levels of anti-apoptotic proteins (eg. Bcl-2) and low levels of pro-apoptotic proteins (eg. p53).