PROGRAMMED CELL DEATH

• introduction to Programmed cell death (PCD),

• To make the student understand apoptosis,

• To explain the mechanism and regulation of Apoptosis

Programmed cell death (PCD), or, can be triggered by a wide range of stimuli, including cell surface receptors like Fas and FasL. It constitutes a system for the removal of unnecessary,aged, or damaged cells that is regulated by the interplay of proapoptotic and antiapoptotic proteins of the Bcl-2 family. The proapoptotic proteins Bax, Bad, Bid, Bik, and Bim conta an a-helical BH3 death domain that fits the hydrophobic BH3 binding pocket on the antiapoptotic proteins Bcl-2 and Bcl-XL forming heterodimers that block the survival-promoting activity of Bcl-2 and Bcl-XL. Thus, the relative abundance of proapoptotic and antiapoptotic proteins determines the susceptibility of the cell to programmed death. The proapoptotic proteins act at the surface of the mitochondrial membrane to decrease the mitochondrial trans-membrane potential and promote leakage of cytochrome c. In the presenc of dATP cytochrome c complexes with and activates Apaf-1.Activated Apaf-1 binds to downstream caspases, such as procaspase-9, and processes them into proteolytically active forms. This begins a caspase cascade resulting in apoptosis.