low temperature protects mammalian cells from apoptosis initiated by various stimuli in vitro

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℃