Central to apoptosis is the utilization of -
Ans. is 'c' i.e., Caspases o Apoptosis is induced by a cascade of molecular events that may be initiated in distinct ways but culminate in the activation of caspases. Caspases are central to the pathogenesis of apoptosis. The process of apoptosis is divided into two phases:i) Initiation phase - During this phase caspases become catalytically activeii) Execution phase - During this phase caspases act to cause cell death.i) Initiation phase of apoptosis# Initiation of apoptosis occurs principally by signals from distinct but convergent pathways.A) Intrinsic (mitochondrial pathway)o In a healthy cell, the outer membrane of its mitochondria displays the proteins BC1-2 and BC1-X. These proteins are antiapoptotic, i.e., they inhibit apoptosis. Internal damage to the cell (e.g., from reactive oxygen species, stress) causes migration of proapoptotic proteins (BaK, Bax and Bim) to the outer membrane of mitochondria at the same time antiapoptotic proteins (BC1-2, BC1-X) are lost from the mitochondrial membrane.o This leads to increase permeability of the mitochondrial membrane. Cytochrome 'C' leaks out from the mitochondria. The released cytochrome 'C' binds to Apaf-1 (apoptosis activating factor-1) in the cytoplasm. These complexes aggregate to from apoptosomes. The apoptosomes bind to an activate Caspase - 9 (initiate caspase).B) Extrinsic or Death receptor pathwayo This pathway is initiated by expression of cell surface death receptors on variety of cells. Death receptors are members of tumor necrosis factor receptor family. The receptors are TNF receptor Type 1(TNFR - 1) and Fas (CD-95). Binding of the complementory death activator, e.g., Fas ligand (Fas L) to Fas and TNF to TNFR-1, transmits a signal to the cytoplasm.o This leads to activation of caspase - 8 (another initiate caspase like caspase - 9). This pathway can be inhibited by an antipoptotic protein FLIP, which can bind to inactive caspases (procaspases) and prevent their activation. So, the final result of both the pathways that is extrinsic receptor mediated pathway and intrinsic mitochondrial pathway is the same i.e. activation of the caspase.ii) Execution phase of apoptosis# In this phase, initiate caspases (Caspase - 8 & 9) activate other caspases known as execution Caspases (Caspases- 3 & 7). After being activated the caspases act on many cellular components.# They cleave cytoskeletal and nuclear matrix proteins and thus disrupts the cytoskeleton. They also lead to the breakdown of the nucleus. In the nucleus the target of caspase activation includes proteins involved in transcription, DNA replication and DNA repair. Caspases activates endonucleases (DNAases) that causes double-stranded breaks in DNA.
Nitrous oxide
Adenyl cyclase
Caspases
c-AMP
Apoptosis