Cell Death Flashcards
Three types of cell death-
Apoptosis, autophagy, necrosis
Necrosis-
largely unregulated; cells “blow up”. Release of cytosolic contents triggers inflammation
largely unregulated; cells “blow up”. Release of cytosolic contents triggers inflammation is called:
Necrosis
Apoptosis-
highly regulated; “programmed cell death”, frequently accompanied by orderly disposal of cell bodies by phagocytosis (neutrophils and macrophages)
highly regulated; “programmed cell death”, frequently accompanied by orderly disposal of cell bodies by phagocytosis (neutrophils and macrophages) is called:
Apoptosis
Autophagy-
highly regulated; actually a cell survival pathway
highly regulated; actually a cell survival pathway is called:
Autophagy
Blebbing-
membrane contained buds formed on cells undergoing apoptosis
membrane contained buds formed on cells undergoing apoptosis are called:
Blebbing
Caspases-
proteases which hydrolyze a large number of proteins during apoptosis
- MSTI (a kinase)- chromatin condensation - ICAD (an inhibitor of a DNase)- DNA cleavage - lamins- nuclear envelope breakdown - Rho kinase- actin cytoskeleton disruption - Cell-cell and cell-ECM adhesion junctions- cell rounding and detachment - golgi and ER proteins- fragmentation of organelles - eIFs- translation arrest
proteases which hydrolyze a large number of proteins during apoptosis
- MSTI (a kinase)- chromatin condensation - ICAD (an inhibitor of a DNase)- DNA cleavage - lamins- nuclear envelope breakdown - Rho kinase- actin cytoskeleton disruption - Cell-cell and cell-ECM adhesion junctions- cell rounding and detachment - golgi and ER proteins- fragmentation of organelles - eIFs- translation arrest
Caspases
Initiator caspases-
9,2,8,10; activated by proteolysis, found in apoptosome, PIDDosome, DISCs
9,2,8,10; activated by proteolysis, found in apoptosome, PIDDosome, DISCs are called:
Initiator caspases
Effector caspases-
3,7,9 also synthesized in inactive form, activated by proteolysis
3,7,9 also synthesized in inactive form, activated by proteolysis are called:
Effector caspases
Caspase cascades-
the substrates of caspases include themselves; once they are proteolytically activated, a caspase can cleave and activate other caspases; thus initiator caspases can activate effector caspases resulting in a great amplification of protease activity
Extrinsic pathway for apoptosis-
ligands, receptors, caspase activation mediate this route; involves signaling molecules of the Tumor Necrosis Factor family, ligand binding form scaffolding for adaptor proteins like FADD which activate and complex with caspases forming DISCs and trigger apoptosis
ligands, receptors, caspase activation mediate this route; involves signaling molecules of the Tumor Necrosis Factor family, ligand binding form scaffolding for adaptor proteins like FADD which activate and complex with caspases forming DISCs and trigger apoptosis
Extrinsic pathway
Intrinsic pathway for apoptosis-
mitochondria, apoptosomes and associated proteins mediate this route; involves damage or stress transmitted to mitochondria resulting in outer membrane pore opening (MOMP) and release of cytochrome C which complexes with APAF-1 and caspase 9 to form the apoptosome
mitochondria, apoptosomes and associated proteins mediate this route; involves damage or stress transmitted to mitochondria resulting in outer membrane pore opening (MOMP) and release of cytochrome C which complexes with APAF-1 and caspase 9 to form the apoptosome
Intrinsic pathway
Coupling of extrinsic and intrinsic pathways-
the two pathways can “cross talk”
Apoptosome-
cytochrome C, APAF-1, and caspase 9; complex for intrinsic pathway of apoptosis
cytochrome C, APAF-1, and caspase 9; complex for intrinsic pathway of apoptosis is called an:
Apoptosome
DISC-
Death Inducing Signaling Complex; composed of FADD and procaspase 8, component of extrinsic pathway of apoptosis
Death Inducing Signaling Complex; composed of FADD and procaspase 8, component of extrinsic pathway of apoptosis is called a:
DISC
Cyctochrome C-
part of apoptosome in intrinsic pathway of apoptosis
APAF-1-
part of apoptosome in intrinsic pathway of apoptosis
FADD-
part of DISC in extrinsic pathway of apoptosis
MOMP-
membrane pore opening in outer mitochondrial membrane due to stress, releases cytochrome C for participation in apoptosome
membrane pore opening in outer mitochondrial membrane due to stress, releases cytochrome C for participation in apoptosome is called:
MOMP
Bcl-2 protein-
centrally important to regulation of apoptosis; inhibit Bax inhibiting formation of MOMP and suppressing apoptosis
centrally important to regulation of apoptosis; inhibit Bax inhibiting formation of MOMP and suppressing apoptosis. this protein is called:
Bcl-2
Bcl-xL-
inhibit MOMP, suppress apoptosis
Bax-
promote MOMP; promote apoptosis. Activated by p53 (DNA damage).
promote MOMP; promote apoptosis. Activated by p53 (DNA damage). This protein is called:
Bax
Bak-
promote MOMP; promote apoptosis
Bid, Bad, Puma, Noxa-
inhibit Bcl-2 and Bcl-xL and promote apoptosis
p53’s role in apoptosis-
activated by Chk1/Chk2 when DNA damage is bad→ activates Bax→ promotes apoptosis and cell death
IAPs-
inhibitor of apoptosis proteins (caspases), can be inhibited by proteins released by mitochondria after MOMP like Smac/Diablo resuming apoptosis
inhibitors of apoptosis proteins (caspases), can be inhibited by proteins released by mitochondria after MOMP like Smac/Diablo resuming apoptosis:
IAPs
Caspase 12-
activated by stress in the ER (excessive unfolded proteins) then activates caspase 9 and the rest of the caspase cascade
Myc-
immediate early transcription factor produces after growth factor signaling; excessive production activates MAPK stress pathway which eventually activates p53→ cell cycle arrest (via upregulation of p21) or apoptosis (via upregulation of Bax)
immediate early transcription factor produces after growth factor signaling; excessive production activates MAPK stress pathway which eventually activates p53→ cell cycle arrest (via upregulation of p21) or apoptosis (via upregulation of Bax)
Myc
Two “survival pathways”-
increased production of Bcl2 to inhibit Bax, or post translational inhibition of pro-apoptotic proteins like Akt kinase
mTor-
inhibits Beclin and Atg# from initiating autophagy, can itself be inhibited by ER stress and/or AMPK (DNA damage) to allow autophagy to destruct damaged cell
inhibits Beclin and Atg# from initiating autophagy, can itself be inhibited by ER stress and/or AMPK (DNA damage) to allow autophagy to destruct damaged cell
mTor-
Beclin 1-
pro-apoptotic protein combines with Atg#’s → autophagy; can be inhibited by Bcl-2 (another reason along with being pro-apoptotic that Bcl-2 is a cell survival and possibly oncogene factor)
pro-apoptotic protein combines with Atg#’s → autophagy; can be inhibited by Bcl-2 (another reason along with being pro-apoptotic that Bcl-2 is a cell survival and possibly oncogene factor)
Beclin 1
Atg#’s-
factors that combine with beclin-1 to induce autophagy
factors that combine with beclin-1 to induce autophagy
Atg#’s
