Biochemistry, Test 3, Quarter 2, Lecture 6

Front 1

What is apoptosis?

Back 1

an intrinsic pathway leading to cell death

Front 2

How do chemotherapy and radiation work to kill cancer?

Back 2

inducing apoptosis

Front 3

What triggers apoptosis?

Back 3

almost anything, several environment agents or withdrawal of growth factors

Front 4

Why is apoptosis better than going necrosis?

Back 4

Apoptosis occurs without inflammation. Necrosis tears down the cellular membrane spilling the contents into the blood.

Front 5

What does the surface membrane look like in a cell which is undergoing apoptosis?

Back 5

blebbing, the membrane becomes assymetrical

Front 6

Describe what happens to the cell structure as it undergoes apoptosis

Back 6

1) chromatin condensation
2) plasma membrane blebbing
3) endonucleolytic cleave of nuclear chromatin
4) cell is fragmented into small vesicles
5) loss of symmetry in the distribution of membrane lipids

Front 7

What signals the macrophage to engulf the cell undergoing apoptosis

Back 7

the membrane flips exposing phosphatidyl serine which signals to macrophages that it needs to be removed

Front 8

What proteases signal apoptosis?

Back 8

caspases

Front 9

What are caspases?

Back 9

cysteine proteases that cleave at aspartate residues

Front 10

Name 2 specific targets for caspases

Back 10

- poly ADP-ribose polymerase (PARP)
- lamins

Front 11

How does apoptosis relate to the cancer lectures?

Back 11

Cancer has some way of halting apoptosis which allows the cancerous cells to just continue growing and infecting

Front 12

Name 3 classic pathways to apoptosis

Back 12

1) withdrawal of growth factors
2) cell surface receptors
3) DNA damage

Front 13

How does removal of growth factors lead to apoptosis?

Back 13

results in the release of cytochrome C and activation of Apafl which activates caspases

Front 14

How do cell surface receptors lead to apoptosis?

Back 14

cell surface receptors such as Fas bind certain molecules and send a signal to activate caspases via FADD

Front 15

How does DNA damage lead to apoptosis?

Back 15

activate a p53 dependent pathway to apoptosis

Front 16

What is bcl-2?

Back 16

an anti-apoptosis gene

Front 17

What is the mechanism of action of bcl-2?

Back 17

it is anchored to membrane and blocks channels which release cytochrome C, thus blocking apoptosis

Front 18

What is bax?

Back 18

Bax is a pro-apoptosis gene

Front 19

What happens if bax is in greater concentration than bcl-2?

Back 19

the cell can undergo apoptosis

Front 20

What is the mechanism of action of bax?

Back 20

it removes the block (bcl-2) and allows cytochrome c to be released and trigger apoptosis

Front 21

How does p53 relate to bcl-2 and bax?

Back 21

p53 is a transcriptional activator of bax
p53 is a transcriptional suppressor of bcl-2

Front 22

What happens if a cell overproduces bcl-2

Back 22

it loses its apoptotic capabilities and it particularly resistant to chemotherapeutic agents

Front 23

What happens to bax/bcl-2 if p53 is mutated?

Back 23

it cannot stimulate the activation of bax and the suppressing of bcl-2 is gone, so anti-apoptosis of the cell occurs

Front 24

What is the bystander effect?

Back 24

This is a concept that has been recognized in which a certain enzyme has been introduced to a small portion of tumor cells, then introduced to the tumor mass, and it has been noted that the entire tumor mass suffers the effects of the enzyme which was introduced into just a few of the cells

Front 25

What enzyme and drug treatment was used to demonstrate the bystander effect in brain tumors?

Back 25

about 10% of the tumor cells were infused with the herpes symplex thymidine kinase enzyme, then reinserted into the tumor. Patient was treated with gangcyclovir which eradicated the tumor (and ONLY the tumor!!!!)

Front 26

What is the major prediction for what causes the bystander effect?

Back 26

the formation of gap junctions through connexons which allow a free exchange of material (including the infused thymidine kinase enzyme) thus making the entire population of cells susceptible to treatment

Front 27

What is mdr-1?

Back 27

a multi-resistance drug which produces p-glycoprotein

Front 28

What is p-glycoprotein?

Back 28

an intrinsic membrane transporter protein which utilizes ATP to pump out hydrophobic molecules from the cell

Front 29

Describe the overall structure of mdr-1

Back 29

it has 12 transmembrane domains and 2 ATP binding sites

Front 30

How have researchers been trying to work around mdr-1? Have they been successful?

Back 30

They have been trying to find a drug that blocks the action of p-glycoprotein. They developed verapamil which blocked activity, however it had its own cardiovascular side effects to contend with

Front 31

Name 2 of the most potent angiogenesis inducers

Back 31

vascular endothelial growth factor
basic fibroblast growth factor

Front 32

Name 4 inhibitors of angiogenesis

Back 32

angiostatin
endostatin
interferons
thrombospondins

Front 33

What is angiostatin a derivative of?

Back 33

a fragment of plasminogen

Front 34

What is the mechanism of action for inducers of angiogenesis

Back 34

act through inducers which activate formation and stimulate infiltration

Front 35

What is neovastat?

Back 35

a naturally occurring inhibitor of angiogenesis taken from shark cartilage which blocks the function of vegf and metalloproteinase activity.

Front 36

What is the mechanism of action of endostatin?

Back 36

it induces tumor endothelial cell death

Front 37

What is endostatin?

Back 37

a proteolytic fragment of collagen type 18

Front 38

What is the mechanism of action for angiostatin

Back 38

inhibits endothelial cell proliferation

Front 39

What is the major advantage to using anti-angiogenesis cancer therapy?

Back 39

drug resistance will be rare because the cells affected are not unstable tumor cells

Front 40

What role does hypoxia play in angiogenesis

Back 40

it is a potent stimulator of the angiogenesis inducers