Mechanisms of muscle plasticity: Genetic & pharmacological manipulations Flashcards
What kind of muscle is PGC1-alpha located?
enriched in slow, oxidative muscles
compared to fast, glycolytic counterparts
What does Transgenic over expression of PGC-1α gene driven by muscle-specific promoter evoke?
significant skeletal muscle remodelling
More red muscles mean?
More capillaries, myoglobin,
What does over-expression of pgc1-alpha do?
more slow oxidative fibers, type I, more red muscle
what regulates oxidative metabolism in muscle?
RIP140
What is RIP140?
transcription repressor
Muscle-specific expression of RIP140 is more expressed where?
high in fast glycolytic muscles, low in slow oxidative
What doe RIP140 knockout mice show?
RIP140 knockout mice (RIP140 KO, RIP140-/-) reveal shift toward slower, oxidative phenotype, redder muscles
wHAT does RIP140 repress?
PPARδ transcriptional activity is repressed by RIP140
What is AICAR?
SYNTHETIC DRUG, gets converted in ZNP in cells, which turns on AMPK (same as AMP), which phosphorlated PGC1-alpha
What does GW do?
gets into cell and turns on PPAR 5 which transcribes genes involved in the metabolism of fat and binds to PGC1-alpha
Some compounds turn on exercise sensitive proteins, what is this called and does it work>
The majority of “exercise mimetics” have targeted metabolic
networks within skeletal muscle. Too good to be true, AMPK makes animals stomachs explode and GW causes cancer
Can there be an exercise pill?
• Multiple integrative regulatory and often redundant pathways have
evolved to detect, respond, and adapt to human movement
• Very complex challenges of designing a pill that might mimic the
extensive range of exercise benefits seen in various tissues and organs
