BMFD 1 Apoptosis

Unprogrammed Cell death

Necrosis

Programmed Apoptotic Cell death

Apoptosis

Programmed Non-Apoptotic Cell death

Autophagy

Plasma membrane during Necrosis:

ruptures & releases cell contents

Plasma membrane during apoptosis:

membrane blabbing & maintains integrity

Nucleus during Necrosis:

some chromatin condensation

Nucleus during apoptosis:

Very distinct chromatin condensation

Other cytoplasmic organelles during Necrosis:

swelling

other cytoplasmic organelles during apoptosis:

minor changes

Necrosis forms __ apoptotic bodies.

no

Apoptosis forms ___ apoptotic bodies.

many

Necrosis ___ cause inflammation.

does

Apoptosis ____ ____ cause inflammation.

does not

Cells commits to necrosis due to ___ ____.

irreparable damage

Possible causes of the irreparable damage are:

poison & toxins, mechanical injuries (cutting, crushing), & physical injuries (radiation)

During Necrosis cells swell due to ___ of normal ____ ____.

loss, ion regulation

Cells contents leak into the ____ ___ & begin the ____ response.

extracellular space, inflammatory

Necrosis causes ____ of cell organelles.

disruption (swelling & leakage)

The organelles that get swelling and leakage include:

ER, lysosomes, mitochondria, nucleus, and Golgi

Membrane blebs are ____ prominent in necrotic cells.

less

Free lysosomal enzymes contribute to the degradation of ____ ___ & _____.

nucleic acids, proteins

Final stage of necrosis is ___ of the plasma membrane.

rupture

The release of ____ cause ___ and activation of immune cells.

decay products, inflammation

Which cell death is the preferred choice?

apoptosis

Apoptosis has two pathways the ___ and the ____.

extrinsic, intrinsic

The extrinsic pathway death signal comes from ___ the cell.

outside

The intrinsic pathways signal comes from ___ the cell.

inside

Death receptors are members of the ____ receptor superfamily.

tumor necrosis factor (TNF)

Death receptors are activated by ___ ___ and may trigger signaling pathways that promote cell ____ or ____.

specific ligands, death, survival

The Fas Ligand binding to the Fas receptor activates the ___ pathway.

Apoptotic

Fas ligand is a ____ proteins belonging to the TNF family.

transmembrane

The Fas Ligand is found on the ___ cell.

Killing

Fas ligand binds to the ____ ____ to induce cell death.

Fas receptor

Fas receptor is found on the ___ cell.

dying

Fas receptor is a member of ___ family.

Tumor necrosis factor (TNF)

Fas receptor is a transmmebrane protein that binds to ____.

Fas Ligand

The intracellular region of ____ contains a ___ ___ that allows recruitment of proteins involved in apoptosis.

Fas Receptor (FasR), death domain

In response to _____, Fas R recruits Fas-Associated death domain (FADD).

Fas Ligand

FADD is an adaptor protein that binds ____ __.

procaspase 8

Caspases are important regulators of ____ _____ ____.

programmed cell death

Caspases are a family of cysteine aspartic acid ___.

proteases

What are the initiator caspases?

Capases 8 & 9

What are the executioner (sometimes called effector) caspases?

Capase 3

Initiator and Executioner cspases are ____ components of the apoptotic pathway.

essential

What type of cells have strong DISC formation and high levels of caspse 8 activation?

Type I cells

High caspase 8 activity leads to high caspase ___ activity.

3

What type of cells have low levels of DISC formation and low levels of caspase 8 activation?

Type II cells

What is one way to amplify the apoptotic signal?

caspase 8 cleaves the protein Bid to generate truncated Bid (T-Bid)

What is the first step of the Extrinsic Pathway?

Cells expressing Fas Ligand (Killing cell) bind to Fas Receptor (on dying cell)

What is the second step of the extrinsic pathway?

Binding of the Fas Ligand & Fas Receptor brings in/exposes Fas- associated death domain (FADD)

What is the third step of the extrinsic pathway?

FADD & procaspase 8 form DISC

Is procaspase 8 inactive or active?

inactive

What is the fourth step in the extrinsic pathway?

Cleavage fo procaspase 8 to caspase 8 to activate.

Is caspase 8 active or inactive?

active

why do you not want caspases to be active when unnecessary?

Due to their initiation of executioner activity & the more executioner activity the more damage

What is the fifth step in the extrinsic pathway?

Caspase 8 cleaves inactive procaspase 3 to generate active caspase 3.

Caspase 3 is the ____.

executioner

Caspase 3 cleaves multiple ____ & ____ proteins necessary for cell survival.

regulatory, structural

Cleavage of the ___ & ___ proteins induce cells to undergo ____.

regulatory, structural, apoptosis

Caspase 3 is the main executioner in which type of cell?

Type I

What is the sixth step in the extrinsic pathway?

Caspase 3 cleaves Inhibitor Caspase Activated DNAse (ICAD) & activates a DNase

ICAD is the inhibitor of ____.

Caspase-activated DNase (CAD)

Active CAD _____ ____ ____ and contributes to nuclei condensation.

degrades chromosomal DNA

Blebbing is a feature of ____.

apoptosis

Blebs are released as ____ ____.

apoptotic bodies

Apoptotic bodies allow for _____.

elimination of the cell without inflammation

p53 activates the ____ family.

BCL-2

Group I of BCL-2 family consists of ____.

Anti-apoptotic proteins (ex. BCL-2)

Groups II & III of BCL-2 family consists of ____.

Pro apoptotic proteins (ex. Bax, Bak, Bad)

BCL-2 gene:

• Inhibits apoptosis

• Prevents apoptosis by inhibiting Bax & Bak association

BAX gene:

• Promotes apoptosis

• Opposes BCL-2 & form pore in mitochondrial outer membrane

BAK gene:

• promotes apoptosis

• opposes BCL-2 and forms pore in the mitochondrial outer membrane

BAD gene:

• pro apoptotic

• Bind BCL-2 making it unable to prevent Bax/Bak interaction

BID gene:

• pro apoptotic

• promotes insertion of BAX into the mitochondrial outer membrane

T Bid goes to the mitochondria & inserts into the ______.

mitochondrial outer membrane (MOM)

T Bid activates ___ & ____ to form pores in the mitochondrial outer membrane.

bax & Bak

Pores in the MOM allow release of _____ into the cytosol.

cytochrome C

Cytochrome c functions in the _______ on the inner mitochondrial membrane.

electron transport

In the cytoplasm, Cytochrome C binds to ___, forming the ____.

Apaf-1, Apoptosome

Procaspase 9 is recruited to the _____ to form caspase 9.

apoptosome

What is the intiator caspase of the intrinsic pathway?

caspase 9

Caspase 9 cleaves and activates procaspase ___ .

3

What is the functional apoptosome made of?

Apaf -1, cytochrome c, caspse 9

BAD binds to ____ breaking contact with bax & bak, allowing them to bind to ___ and begin to form pores in the MOM.

BCL-2, t-bid

Externalization of _______ is a hallmark of apoptosis.

phosphotidylserine

Apoptosis is important in tissue ___ and ____.

development, homeostasis

What is autophagy?

cellular process where damaged or unnecessary organelles are deliver to lysosomes for degradation into basic building blocks

Autophagy can ____ ____ or cause ___.

recycle cellular components, cell death