Cell Bio Final: Apoptosis

Apoptosis

Programmed cell death

• regulates cell numbers in animals

Apoptosis in development

can remove cells that are not needed

ex. paws/hands; start as spade like structures and only become individual/seperate b/c cells bw die during embryonic development

apoptosis characteristics

–Neat, cells shrink and condense

–Well regulated response to balance cell division

–Dying cells don’t damage healthy neighbors

—Cell surface markers attract macrophages

Necrosis

–Messy, cells appear to swell and burst

–Usually caused by acute injury

–Can trigger damaging inflammatory response

Caspases

•Family of proteases responsible for apoptosis

•Exist in cell as inactive procaspases

•Two types (work together)

–Initiator caspases

—Executioner caspases

Initiator caspases

cleave and activate executioner caspases

executioner caspases

dismember numerous key proteins important for maintaining the cell's structure and function

procapase activation

procaspase= capspase

done by cleavage

• the inactivate procaspase starts at dimer

• undergoes cleavage, releasing inhibitory fragments (prodomains)

  • adopts active conformation, ready for binding with executioner to start cascade toward apoptosis

Apoptosis is mediated by…

proteolytic cascade ( irreversable, apoptosis regulated to make sure necessary)

• a chain reaction of caspases that activate each other to execute programmed cell death (apoptosis) (cleave important proteins)

Initiation of apoptosis

•Extracellular (Extrinsic) pathway

–Signal comes from another cell

–Signal received by Fas (death receptor)

•Intrinsic pathway

–Signal comes from inside the cell in response to DNA damage or other injury

–Mediated by Bcl2 family members

•Extracellular (Extrinsic) pathway

-signals come from another cell (ligand) binds to death receptors (FAS)

-triggering a cascade that activates DISC (death-inducing signaling complex), which includes initiator complex (procaspase 8/10)

-when initiator (8/10) is activated, it activated executioner caspase and starts caspase cascade = apoptosis

Intrinsic apoptotic pathway

-Bak and Bax proteins are activated by apoptosis stimulus (in the outer mitochondrial membrane)

-leads to release of cytochrome C

-Cytochrome C binds to an adaptor protein

-assembles into apoptosome (7 armed complex) which recuits 7 molceules of an initiator caspase (Caspase-9)

-activation of the procaspase 9 (which activates executioner caspases)

-starts caspase cascade toward apoptosis

Bcl2 Family Members

•Regulate activation of caspases

Bax and BaK

induce apoptosis, triggered by DNA damage or injury

Bcl2

inhibits apoptosis, can receive survival signals from pathways like Akt