Histology/Cell Biology Flashcards
(20 cards)
Name 9 targets of Apoptosis that occur in the body.
For example, infected cells are killing via apoptosis by NK/CD8-T cells.
- Infected cells
- Thymocytes that recognize self in Thymus
- DNA damaged cells (ie - p53 triggers apoptosis during cell cycle)
- Unecessary cells during development (ie - finger/toe formation)
- Excess/Obsolete Cells (neurons that are not used in brain)
- Tissue involution (shrinkage) due to l_oss of growth factors_. (ie - uterus after pregnancy)
- Chemotherapeutic Killing
- _Defective Lymphocytes _
- _Damaged Cell_s - Hypoxic, Nutrient deficient, etc.
What are some morpholigica features of apoptotic cells?
- Chromatin Condensation
- Progressive Cell shrinkage
- Nuclear Shrinkage (pyknosis)
- Nuclear Fragmentation (karyorrhexis)
- Plasma Membrane Blebbing
- Apoptotic Bodies (vesicle-like bodies shedding from cell) - these are phagocytosed
- Phagocytosis without inflammation
Name 3 disease linked to suppression of Apoptosis.
- Cancer
- Atherosclerosis
- Autoimmune disorders
Name 5 diseases linked to increased apoptosis.
- Viral Infections (AIDS)
- Neurodegenerative Diseases (Alzheimers)
- Multiple Sclerosis
- Ischemi Injuries (myocardial infaction)
- Toxic-induced diseases (alcohol-induced hepatitis)
How many total proteins make up the apoptosis genes (both pro and anti apoptotic)?
How many are pro and how many are anti?
What are the family of proteins called?
24 total protiens
- 6 anti-apoptotic
- 18 pro-apoptotic
Bcl-2 Family Regulatory Proteins
What are the 2 main protein families involved in being pro-apoptotic?
- BH3-only
- Bax Family
Name at 3 proteins in the Bax family?
Bax, Bak, Box
Name 8 proteins in the BH3-only family
Bid, Bim, Bik
Bad, Bmf, Hrk
Noxa, Puma
Name 5 proteins in the Anti-apoptitic family.
Bcl-2, Bcl-X, A1, Bcl-w, Mcl-1
Which BH3-only protein does Granzyme B and/or Death receptors trigger
Bid
An intrinsic apoptotic signal (ie-DNA damage) will release sequestered ________ proteins which will release sequested ________ proteins from _______ proteins. The ________ proteins will then create channels in mitochondria which releases ____________.
An apoptotic signal (ie-DNA damage) will release sequestered BH3-ONLY proteins which will release sequested BAK proteins from BCL-2 proteins. The BAK proteins will then create channels in mitochondria which releases CYTOCHROME C.
During an intrinsic apoptotic event, _________ is released from the mitochondria where it binds to ________. _________ then binds to that molecule forming a _________ initiator. The _________ initiator then triggers a ________ effector which degrades the cellular components.
During an intrinsic apoptotic event, Cytohrome C** is released from the mitochondria where it binds to **Apaf-1. Procaspase-9 then binds to that molecule forming a caspase initiator. The caspase initiator then triggers a caspase effector which degrades the cellular components.
What do IAPs inhibit?
Ihibitor of Apoptosis (IAPs) are proteins that inhibit caspases.
What does Smac inhibit?
Smac (aka -Diablo) inhibits IAPs. It is released with cytochrome C during an apoptotic event. It allows apoptosis to occur.
How many human caspases are there?
14
- 4 initiators (2,8,9,10)
- 3 effectors (3,6,7)
- 7 others not related to apoptosis
Can withdrawl of certain growth factors trigger apoptosis?
Yes.
PI3K-Akt pathway is stimulated by growth factors like insulin. Akt inactivates Bad which usually trigger apoptosis.
What are the 2 extrinsic apoptotic pathways?
- Death Receptors
- Granzyme B
During extrinsic apoptosis, a ligand binds to a death receptor. The death receptors intracelluar domain, called the _____ ______ binds to a _________ (FADD). The FADD’s second domain called the _____ ____ domain recruits _________ and allows for its activation.
During extrinsic apoptosis, a ligand binds to a death receptor. The death receptors intracelluar domain, called the death domain binds to a Fas-Associated Death Domain (FADD). The FADD second domain called the death effector domain recruits procaspase-8 and allows for its activation.
How does the Granzyme B pathway work in apoptosis?
What other molecule is usually associated with the release of Granzyme B?
Which cell types release it?
Granzyme B is released from Cytotoxic T-Cells and NK cells.
Granzyme B is released with another protein called perforin. Perforin puts holes in the cellular membrane. Granzyme B then activates BH3-only protein Bid. It can also directly activate procaspase 3 and 8.
Does cytochrome C ALWAYS need to be activated to trigger apoptosis?
No.
Death receptors and granzyme B pathways can trigger effector capsases without the use of cytochrome C and caspase 9.
