bio 202 lecture 15 cell death

apoptosis

programmed cell death, cells removed without damaging neighbors or rest of tissue

cell death reasons

• disease/damage

• development

• maintianing tissue

disease/damaged cell examples

virus-infected, DNA damage (with potential for mutation)

death during development

determine size/shape of tissues

• die to remove unneeded structures (frog tail)

• cells between digits during embryonic dev

• excess neurons die

how fast can apoptotic cells be cleared from mouse digits

1 day apart!

nervous system apoptosis

target cells secrete ‘survival factors’

• cells that recieve enough live, cells that don’t undergo apaptosis'

• matches number of target cells in system

purpose of survivial factors in apoptosis

matches number of target cells in system

how does cancer arise?

imabalance between cell division and apoptosis

necrosis

death in response to an insult (ex. cut, lack of blood supply)

• cells swell, burst, and spill

• leakage of enzymes can damage nearby cells

• often triggers inflammatory response

apoptosis

• cell shrinks, cytoskeleton collapses, nuclear envelope disassembles

• DNA fragments

• cell surface chemically altered

• dying cell breaks into membrane-enclosed fragments

how are caspases made?

as inactive pro-caspases

are inititor procaspases monomers or dimers?

inactive monomers, adapter proteins facilitate dimerization

are executioner procaspases monomers or dimers?

dimers, don’t need adapter proteins

proteins cleaved by caspases

• nuclear lamins, breakdown nuclear envelope

• components of cytoskeleton

• cell-cell adhesion proteins

CAD

• nuclease that can cut up DNA

• normally bound by inhibitor iCAD

iCAD in apoptosis

executioner caspase cleaves iCAD to activate CAD

extrinsic apoptosis

external signals tell the cell to die

intrinsic apoptosis

cell itself recognizes problem (mitochondrial pathway)

extrinsic pathway

• death (Fas) receptors activated by Fas ligand on killer lynphocytes

• induces formation of DISC in damaged cell

what does DISC do

triggers cross-cleavage of caspase 8

intrinsic pathway

• mitochondria release cyt C

• cytosolic cyt C activates adaptor protein that leads to apoptosome assmebly

• apoptosome forms, recruits procaspase 9

survivial factors

• cells don’t die until they really need to

• bind cell surface receptors

• triggers signaling cascade that activates a TF

how do survival factors inhibit apoptosis?

bind cell surface receptor, transcripes BCl2, an anti-apoptotic protein

BCl2 family

contains pro and anti apoptotic proteins

how does BCl2 block apoptosis?

antagonizes Bax/Bak

Bax/Bak function

mediates release cyt c into cytoplasm

too much apoptosis

heart attacks, strokes from lack of oxygen

too little apoptosis

many cancers

• some overproduce anti-apop protein BCl2