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

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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

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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 Presentation

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Page 1: 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

Page 2: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

Outlines

1. Background :

a. Apoptosis extrinsic & intrinsic pathway

b. Mild hypothermia therapy

2. Results

3. Discussion

4.

Page 3: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

Extrinsic pathway ( Death receptors )

Page 4: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

Intrinsic pathway( Mitochondria-dependent )

Page 5: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

Intrinsic Extrinsic

Modified apoptosis pathway

Page 6: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

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.

Page 7: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

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.

Page 8: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

Effects of hypothermia on Thapsigargin-induced apoptosis ( ER stress )

Thapsigargin:An inhibitor of Endoplasmic reticulum ( ER ) Ca+2 ATPase pumps

37℃

32℃

Page 9: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

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

Page 10: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

Intrinsic Extrinsic

Modified apoptosis pathway

Page 11: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

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

Page 12: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

Molecular mechanism of hypothermia on Adriamycin-induced apoptosis ( DNA damage )

Bcl-xL:anti-apoptotic Bcl-2family of protein

32℃

37℃

Page 13: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

Intrinsic Extrinsic

Modified apoptosis pathway

Page 14: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro

Effect of hypothermia on the level of p53

P53 transcript

MG132:A proteasome inhibitor

32℃

37℃37℃

32℃

Page 15: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro
Page 16: Low temperature protects mammalian cells from apoptosis  initiated by various stimuli in vitro