low temperature protects mammalian cells from apoptosis initiated by various stimuli in vitro
DESCRIPTION
Low temperature protects mammalian cells from apoptosis initiated by various stimuli in vitro. Authors: Toshiharu Sakuraia, Katsuhiko Itoha, Yu Liua, Hiroaki Higashitsujia, Yasuhiko Sumitomoa, Kazuhiro Sakamakib, Jun Fujita. - PowerPoint PPT PresentationTRANSCRIPT
Low temperature protects mammalian cells from apoptosis initiated by various stimuli in vitro
Authors: Toshiharu Sakuraia, Katsuhiko Itoha, Yu Liua, Hiroaki Higashitsujia, Yasuhiko Sumitomoa, Kazuhiro Sakamakib, Jun Fujita.
Source: Experimental Cell Research 309 (2005) 264 – 272
Outlines
1. Background :
a. Apoptosis extrinsic & intrinsic pathway
b. Mild hypothermia therapy
2. Results
3. Discussion
4.
Extrinsic pathway ( Death receptors )
Intrinsic pathway( Mitochondria-dependent )
Intrinsic Extrinsic
Modified apoptosis pathway
Mild hypothermia therapy
A. K. Kataoka, H. Yanase, Mild hypothermia—A revived countermeasure against ischemic neuronal damages, Neurosci. Res. 32 (1998) 103– 117.
B. S.A. Bernard,etc. , Treatment of comatose survivors of out-of hospital cardiac arrest with induced hypothermia, N. Engl. J. Med. 346 (2002) 557– 563.
C. F. Shann, Hypothermia for traumatic brain injury: how soon, how cold, and how long? Lancet 362 (2003) 1950– 1951.
D. M.F. Hong, P. Dorian, Update on advanced life support and resuscitation techniques, Curr. Opin. Cardiol. 20 (2005) 1 – 6.
Aim
a. Hypothermia ( 32 ) protects cells from apoptosis induced by a variety ℃of stress conditions ( ER , DNA damage & Fas-mediated stresses )
b. Hypothermia molecular mechanism.
Effects of hypothermia on Thapsigargin-induced apoptosis ( ER stress )
Thapsigargin:An inhibitor of Endoplasmic reticulum ( ER ) Ca+2 ATPase pumps
37℃
32℃
DNA damage
Inhibition of
topoisomerases Osmotic stress
Oxidative stress Fas-mediated
37℃
32℃
37℃
32℃
Effects of hypothermia on cell death induced by various stresses
Intrinsic Extrinsic
Modified apoptosis pathway
Molecular mechanism of hypothermia on Thapsigargin-induced apoptosis ( ER stress )
32℃
37℃
Protein translocation
p53 -/-/ Mdm2 -/- cells
Anti-apoptotic effects of hypothermia on thapsigargin-treated cells are p53-independent
Molecular mechanism of hypothermia on Adriamycin-induced apoptosis ( DNA damage )
Bcl-xL:anti-apoptotic Bcl-2family of protein
32℃
37℃
Intrinsic Extrinsic
Modified apoptosis pathway
Effect of hypothermia on the level of p53
P53 transcript
MG132:A proteasome inhibitor
32℃
37℃37℃
32℃