Cell death Flashcards
Caspases
- cysteine-aspartic proteases
- chief executioners of apoptosis
- induce both apoptosis pathways when activated
Caspases pathway (2)
Receptor mediated (extrinsic pathway) Mitochondria mediated (intrinsic pathway)
The intrinsic caspases pathway activated by?
activated by a variety of cell stresses such as free radical damage, DNA damage, viral infection, or loss of survival signals.
Importance of apoptosis
Embryo development – sculpting tissue
Immune system – destroying self-reacting immune cells.
Immune system – destroying virus infected cells.
Homeostasis – as a counter-balance to cell division and removal of old or damaged cells.
Cancer – radiotherapy and most chemotherapy drugs work by inducing apoptosis. Many cancer cells have defects in the apoptosis pathways that make them resistant to apoptosis.
Types of cell death
Necrosis (uncontrolled cell death) - Associated with disease.
Apoptosis (programmed cell death or cell suicide) - essential part of normal health and development.
In average, adult has how many cells die through apoptosis/ day
between 50 and 70 billion cells. (In a year your entire body weight of cells will have died through apoptosis.)
A family of how many proteases that exist as ___________ in cells.
12 proteases
exist as inactive pro-enzymes
How to activate other caspases ?
Following activation by cleavage they can activate other caspases in a cascade.
Two types of apoptotic caspases
initiator caspases- activate other caspases.
effector (executioner) caspases -break down cellular components such as the cytoskeleton and DNA.
Can the process of apoptosis be reversed and terminated ?
Activation of caspases is the point of no return in the process of apoptosis.
Flip over of _________ from the ________ lipid layer to the ______ layer acts as a _____ signal to ________, which will destroy the apoptotic cell
Flip-over of phosphatidylserine from the inner lipid layer to the outer layer acts as an “eat me” signal to macrophages, which will destroy the apoptotic cell
In the intrinsic apoptosis pathway, pores form in the _____mitochondrial membrane allowing release of _______ _____into the ________, acts as a ______ for apoptosis.
outer mitochondrial membrane
allowing release of cytochrome C into the cytosol
act as a trigger
what is apoptosome?
the formation require?
a multi-protein complex formed by cytochrome C binds to other cytosolic proteins Apaf-1, pro-caspase 9 and the formation require ATP.
the complete apoptosome has how many protein ?
the molecular weight?
How to activate?
There are 7 molecules of each protein (cytochrome C, Apaf-1, pro-caspase 9) in the complete apoptosome
A combined molecular weight of 700 KDa.
The end result is the cleavage and therefore activation of pro-caspase 9 into active caspase 9, an initiator caspase.
difference between pro-caspase 9 into active caspase 9
caspase 9- an initiator caspase, activated by cleavage of pro-caspase 9 - inactive form
What controls the releasing of cytochrome C from the mitochondria
The Bcl-2 family of proteins
How many members in the Bcl-2 family of proteins
- around 20 members
- consist of both pro-apoptotic and anti-apoptotic proteins.
The Bcl-2 proteins family’s ability of inducing apoptosis depends on_______
Their ability to induce apoptosis depends on the balance between the two types.
Pro-apoptotic members of the Bcl-2 family
are thought to work by inserting themselves into the mitochondrial surface and promoting the formation of large pores in the outer membrane that leads to the release of Cytochrome C.
Anti-apoptotic members of the Bcl-2 family
are thought to exist in the mitochondrial outer membrane and act to block the action of the pro-apoptotic members.
