Programmed Cell Death and Aging

Question 1

What family of genes encodes proteins that signal and regulate autophagy?

Answer 1

ATG family of genes

Question 2

What are the pathways to apotosis and include which involve mitochondria and which do not

Answer 2

Do not involve mito - Extrinsic and Stress-activated (ceramide), Do involve Mito - Granzyme/perforin and Instrinsic

Question 3

Give the sequence of receptor-activated apoptosis

Answer 3

Ligand to Receptor to Docking protein to Caspase 8 to Caspase 3

Question 4

What does caspase 3 do when activated?

Answer 4

Activates endonucleases to cleave DNA as well as enzymes that digest nuclear proteins and cytoskeletal proteins

Question 5

What do lymphocytes use to make a hole in target cell membranes?

Answer 5

Perforin

Question 6

What do lymphocytes pass into target cells through perforin created holes, and what does this enzyme do?

Answer 6

Granzyme, which activates procaspase 10 to caspase 10

Question 7

What three pro-apoptotic effects does granzyme have on a cell?

Answer 7

1) Activation of caspase-3, 2) Activation of DNA-nicking enzymes, 3) Alteration of Bax and Bak balance at mitochondrial membranes

Question 8

List the steps in the ceramide pathway to apoptosis

Answer 8

Stress to Nitric Oxide Synthase (NOS) to NO radical to Sphingomyelinase to Ceramide to Stress-activated Protein Kinase (SAPK) to Caspase 8 to Caspase 3

Question 9

Anti-apoptotic Bcl-2 family proteins

Answer 9

Bcl-2, Bcl-XL, Ku-70

Question 10

Pro-apoptotic Bcl-2 family proteins

Answer 10

Bax, Bak, Bam, Bad, Bim, Puma

Question 11

What alters the Bcl-2 family balance in response to DNA damage to activate apoptosis?

Answer 11

p53

Question 12

What do Bax and Bak do when freed and what is the effect of this?

Answer 12

Activate the Mitochondroal Permeability Transition Pore (MPTP), which allows cytochrome c to exit into the cytosol

Question 13

What is the effect of cytochrome c in the cytosol

Answer 13

It activates Apaf-1, which activates caspase 9, which activates caspase 3

Question 14

Besides Bcl-2 activation, what is another way the MPTP can be opened?

Answer 14

By calcium release from ER

Question 15

What is the effect of aging on cross-linking of proteins in the ECM?

Answer 15

Aging is associated with increased cross-linking

Question 16

Sequence of telomeres and which end of the chromosomes are they at?

Answer 16

TTAGGG, they are at the 3 prime end of the chromosome

Question 17

What family of enzymes is activated by calorie restriction and what is the effect of their activation?

Answer 17

Sirtuins (NAD-dependent de-acetylases) which increase survival, stress response, and Ku70 (anti-apoptotic), and decrease in p53

Question 18

What is the relationship between calorie consumption, mTOR, and oxidant damage?

Answer 18

mTOR is increased when consuming a lot of calories, and increased mTOR yields more oxidant damage

Question 19

What protein is p53 normally complexed with and what type of protein is it?

Answer 19

MDM2, an E3-ubiquitin ligase

Question 20

Three mitotic inhibitors

Answer 20

p14ARF, p16INK4A, and p53

Question 21

What is the relationship between superoxide dismutase expression, catalase expression, and longevity?

Answer 21

Enhanced expression of superoxide dismutase and catalase are associated with increased longevity

Question 22

Cokayne syndrome

Answer 22

A disease of premature aging related to a defect in DNA repair

Question 23

What is the TORCH complex?

Answer 23

Toxoplasmosis Other Rubella Cytomegalovirus Herpes