Apoptosis Mech Lec 3 Flashcards
What are two ways in which cells die?
- necrosis(massive death) (inflam)all die at one time
- apoptosis / PCD- intrinsic to the cell, under genetic control(no inflammation)
process where single cells activate and intrinsic death program to kill themselves
What are normal responses to physiological stimuli?
A. fetal development
1. removing webbing between fingers
2. male or female reproductive organs
3. after infancy: shrinkage of thymus glands
B. Adulthood
1. menstrual shed
2. autoimmune cells
3.aging cells
4. cells turnover in intestinal crypts
What are pathological situations apoptosis occurs in?
- infected or injured cells(HIV, HepB)
- cells with DNA damage(radiation, drugs, birth defects)
3.cancer(chemo) - transplant rejections
What makes a cell decide to commit suicide?
- the withdrawal of positive signals (needed for survival)
-growth factor for neurons
-interlukin -2 for lymphocytes - the receipt of neg signals
-TNF(Tumor necrosis factor)
-FAS Ligand (CD95)
What are mech of PCD:
A. intrinsic mitochondrial pathway
-DNA damage and p53
-involves mitochondria/ cytochrome C and AIF that activate Caspase 9
B. External signal
-FAS-L and TNF bind to their receptors on the target cell
-transmit a signal to the cytoplasm
activates Caspase 8
C. Apoptosis Inducing Factor
-unique in the neural apoptosis, no caspases involved
What are the ultimate executioners of PCD?
Caspases; cleave 100 diff cell target proteins
-the activation of an initiator caspase starts a chain reaction of caspase activation leading to death
What is the regulation of Apoptosis:
BcL : family of proteins reside mainly in the mitochondria
-Anti-apoptotic: BcL-2, BcL-xl
-Pro-apoptotic: Bax, Bad
-overexpressing of BcL- 2 gene will inhibit the apoptosis
Cytotoxic T cells /natural killer cells order the infected cells to PCD
-certain viruses have apoptosis brake genes inhibit the infected cells from committing suicide
2. mebrane bulges-bleb
3. nuclear mebranes breaks: endonucleases clip chromosomes (at histones linker region, about 180-200 base pair interval)….nucleus may break up into 2 or more fragments
4. cell fragments produce apoptotic bodies
5. phagocytosis(macrophages) or adjacent
What is p53 gene:
tumor Suppressor gene: regulates cell division by keeping cells from dividing or replicating too fast or in an uncontrolled way
Bcl protein- makes sure to regulate apoptosis
What is the future of PCD:
increased apoptosis seen in:
Azheimers
viral infections
graft infection
Decreased apoptosis seen in:
autoimmune diseases-arthritis
cancer
AIDS-CD4 T-cells less than 1 in 100,000 cells are infected most of the cells that die are uninfected
aging