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20170927進階分子細胞生物學林常申老師_How cells respond to damage and stress (damage &…
20170927
進階分子細胞生物學
林常申老師_How cells respond to damage and stress
damage & stress key words
Genotoxic stress
Oxidative stress
Nutrient deprivation
metabolic stress
protein misfolding
ER stress
Consequence / cell outcome
Telomere shortening
Telomere shortening due to cell proliferation
telomere dystunction
telomere erosion or damage
DNA damage signal
p53 & p16INX4a/Rb
Senescence (EMBO (2011) 30, 2520-2531)
老化其實是一個不可逆的反應
p53 but not p16INX4a/Rb
Apoptosis
nether p16INX4a/Rb nor p53
Genomic instability
既不會老化也不會死亡，常在cancer cell看到的現象
Stress and resilience
小孩子在幼年的時候有受到比較大的傷害，會使telomere長度縮短
如果母親在環運過程受到一些stress的暴露會造成小孩壽命較短
Cell response/signaling
Damage/stress
repair / defense / recover
if unresolved : induce cell death
Ex : apoptosis induce by
DNA damage
Stress response in normal aging vs. Alzhemer disease
http://www.sciencedirect.com/science/article/pii/
DDR→repair pathway (Nature Review cancer 12:801-817 (2012))
Targeting DDR as a theraprutic strategy
DNA damage會有sensor proteins去告知細胞需要對此damage response
以cell cycle來說會被停在G/S與G2/M兩階段
Gene therapy: BRCA & PARP
resistance的產生讓治療過程變困難
The role of p53 in tress response
nature Review cancer 9:749-758 (2009)
