Lecture 17 Flashcards
HIF-1 α is
Hypoxia-Inducible factor, transcription factor causes bunch of genes to be expressed. monitor of low oxygen, increased glycolysis.
Oxygen’s role in cancer
cancer cells grow rapidly and are starved for oxygen, they respond by inducing HIF-1α to recruit blood vessels for the cells
angeogenesis meaning
production & migration of blood vessels
Warburg effect
differentiated tissues glucose metabolized in oxygen dependent way, lots of ATP per glucose molecule. the tumor will use glucose without spending oxygen and giving off lactate. Mitochondria is messed up?
current view about why cancer cells don’t metabolize glucose all the way to CO2
cells are highly anabolic and they use glucose to make carbon skeletons that are then used to make other stuff. They do Pentose phosphate pathway, synthesize AA.
1953 Sydney Winehouse’s idea of cancer cells
Tumor cells derive nearly all their fatty acids from de novo synthesis (derived from little things)
role of citrate lyase in cancer cell growth
an anabolic carbon source (make FA of cholesterol) allows for cancer cell growth
isositrate dehydrogenase role in cancer cells
IDH: creates αKG
then mutant gene R132 (arginine) reduces αKG
new metabolic pathway that creates 2-hydroxyglluterase (2-OH-GLU)
mitochondria’s role in apoptosis
releases cytochrome-C, which is critical in triggering apoptosis
what is CR?
caloric restriction
why is CR important in aging?
Caloric Restriction is the main way to extend longevity
What is ROS
Reactive Oxigen Species
various molecules generated in mitochondria, very reactive
Two types of ROS
oxidative stress: leak of electros to oxygen
peroxide, oxide anion
damage mitochondria, macromolecules
Role of mitochondria in ROS production
ROS molecules are generated in mitochondria, increased caloric intake, increases the producion.
the other thing, is that these eventually do a positive feedback on mitochondria, increasing the production even more
DAF2 is ____
insulin receptor homologue
how do changes in insulin signaling affect ageing?
since insulin signals the prescence of food, maybe it makes us do things that make us age faster. So if we get rid of the ability to respond to those signals, maybe we can live longer.
if C. elegans loose DAF2, what happens?
loss of DAF2 leads to increased longevity on C. elegans
loss of mitochondrial function leads to ____ in C. elegans
increased longevity
what are EAT genes?
genetic version of caloric restriction
what do EAT genes do in C. elegans?
they alter the rate of muscle contraction (which is the way C. elegans eat) leading to restricted caloric intake ⇒ overall increased longevity
What are SIR2?
Silent Information Regulation, a longevity gene in yeast:
NAD+ dependent protein, removes acetyl groups, only when NAD is at certain levels
indicator of energy charge in cells
what are STACS
SIR Two Activating Compounds
looking for drug that activates SIR2
one of the first SIR2 molecules discovered
resveratrol, a natural activator or SIR2 present in wine
great antioxidant!
