Apoptosis

Apoptosis- (Programmed cell death )It is a natural way in which  the cell kill itself. 

1.In situations like infection, inflammalation it is necessary.
2.In metastasis process of cancer to prevent the rapid growth of uncontrol cells apoptosis occur.
Changes -
1.Cell shrinkage 
2.Chromatin condensation
3.Membrane blebbing 
4.Nuclear collapse 

Types-
1.Intrinsic (the origin is from inner side of cell)
2.Extrinsic(pathway originated outside the cell)

1.  Intrinsic or mitochondrial pathway-

• In a normal cell, the outer membranes of mitochondria display the protein Bcl-2 on their surface. Bcl-2 inhibits apoptosis.
• Internal damage to the cell caused by protein Bax, to migrate to the surface of the mitochondria where it inhibits the protective effect of Bcl-2 and inserts itself into the outer mitochondrial membrane punching holes in it and causing cytochrome c to leak out.
• The released cytochrome c binds to the protein Apaf-1 ("apoptotic protease activating factor-1") using the energy provided by ATP,these complexes aggregate to form apoptosomes.
• The apoptosomes bind to and activate caspase-9.
• Caspase-9 is one of a family of caspases which are all proteases. They get their name as they cleave proteins for example in aspartic acid (Asp) residues.
• Caspase-9 cleaves and, in doing so, activates other caspases (caspase 3 and 7).
• The activation of these  caspases creates an expanding cascade of proteolytic activity which leads to
  • digestion of structural proteins in the cytoplasm,
  • degradation of chromosomal DNA, and phagocytosis of the cell.

2.  The extrinsic or death receptor pathway-

• Fas and the TNF receptor are integral membrane proteins with their receptor domains exposed at the surface of the cell 
• Binding of complementary death activator (FasL and TNF respectively) transmits a signal to the cytoplasm that leads to-activation of caspase 8
• Caspase 8 (like caspase 9) initiates a cascade of caspase activation leading to phagocytosis of the cell.

 When cytotoxic T cells recognize their target,

• they produce more FasL at their surface.
• This binds with the Fas on the surface of the target cell leading to its death by apoptosis.

                               Image source- http://www.nature.com/nrm/journal/v9/n1/fig_tab/nrm2308_F2.html

1.Apoptosis all are seen except
a necrosis
b. cell shrinking
c. nuclear clumping
d. inflammation                                                                          Ans.d

2.Starting point of apoptosis for programme cell death is -
a)Activation of endonuclease
b)Release of enzyme
c)Accumulation of calcium
d)Destruction by macrophages                                                    And.a

3.Chemotherapeutic drugs can cause:
A. Only necrosis
B. Only apoptosis
C. Both necrosis and apoptosis
D. Anoikis                                                                                 Ans.C

4.Annexin V assay is a method to detect?
a) Necrosis
b) Apoptosis
c) Inflammation
d) Neoplasia                                                                             Ans.B

5.Radiotherapy in tumor cells induces
a. Necrosis
b. Apoptosis
c. Phagocytosis 
d. Both necrosis and apoptosis                                                                      Ans.B(Radiation therapy causes apoptosis of tumors and surrounding tissue via free radical formation and dsDNA breakage.)

6.In apoptosis, Apaf-I is activated by release of which of
the following substances from the mitochondria?
(a) Bcl-2 
(b) Bax
(c) Bcl-XL
(d) Cytochrome C                                                                         Ans.D

7.Organelle that plays a pivotal role in apoptosis:
A. Endoplasmic reticulum
B. Golgi complex
C. Mitochondria
D. Nucleus                                                                                 Ans.C

8.Mechanism of mammalian apoptosis involves the most impor- tant role of the following protein:
A. Receptor for TNF 
B. BCL-2
C. TP53
D. CED-9                                                                                      Ans.B

NOTE-Apoptosis occurs in all ( Embryogenesis ,Menstruation ,Tumors ,Viral infection)

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