Programmed Cell Death and Aging Flashcards
What family of genes encodes proteins that signal and regulate autophagy?
ATG family of genes
What are the pathways to apotosis and include which involve mitochondria and which do not
Do not involve mito - Extrinsic and Stress-activated (ceramide), Do involve Mito - Granzyme/perforin and Instrinsic
Give the sequence of receptor-activated apoptosis
Ligand to Receptor to Docking protein to Caspase 8 to Caspase 3
What does caspase 3 do when activated?
Activates endonucleases to cleave DNA as well as enzymes that digest nuclear proteins and cytoskeletal proteins
What do lymphocytes use to make a hole in target cell membranes?
Perforin
What do lymphocytes pass into target cells through perforin created holes, and what does this enzyme do?
Granzyme, which activates procaspase 10 to caspase 10
What three pro-apoptotic effects does granzyme have on a cell?
1) Activation of caspase-3, 2) Activation of DNA-nicking enzymes, 3) Alteration of Bax and Bak balance at mitochondrial membranes
List the steps in the ceramide pathway to apoptosis
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
Anti-apoptotic Bcl-2 family proteins
Bcl-2, Bcl-XL, Ku-70
Pro-apoptotic Bcl-2 family proteins
Bax, Bak, Bam, Bad, Bim, Puma
What alters the Bcl-2 family balance in response to DNA damage to activate apoptosis?
p53
What do Bax and Bak do when freed and what is the effect of this?
Activate the Mitochondroal Permeability Transition Pore (MPTP), which allows cytochrome c to exit into the cytosol
What is the effect of cytochrome c in the cytosol
It activates Apaf-1, which activates caspase 9, which activates caspase 3
Besides Bcl-2 activation, what is another way the MPTP can be opened?
By calcium release from ER
What is the effect of aging on cross-linking of proteins in the ECM?
Aging is associated with increased cross-linking
Sequence of telomeres and which end of the chromosomes are they at?
TTAGGG, they are at the 3 prime end of the chromosome
What family of enzymes is activated by calorie restriction and what is the effect of their activation?
Sirtuins (NAD-dependent de-acetylases) which increase survival, stress response, and Ku70 (anti-apoptotic), and decrease in p53
What is the relationship between calorie consumption, mTOR, and oxidant damage?
mTOR is increased when consuming a lot of calories, and increased mTOR yields more oxidant damage
What protein is p53 normally complexed with and what type of protein is it?
MDM2, an E3-ubiquitin ligase
Three mitotic inhibitors
p14ARF, p16INK4A, and p53
What is the relationship between superoxide dismutase expression, catalase expression, and longevity?
Enhanced expression of superoxide dismutase and catalase are associated with increased longevity
Cokayne syndrome
A disease of premature aging related to a defect in DNA repair
What is the TORCH complex?
Toxoplasmosis Other Rubella Cytomegalovirus Herpes
