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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.

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

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  1. 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

  2. Outlines 1. Background : a. Apoptosis extrinsic & intrinsic pathway b. Mild hypothermia therapy 2. Results 3. Discussion 4.

  3. Extrinsic pathway ( Death receptors )

  4. Intrinsic pathway ( Mitochondria-dependent )

  5. Modified apoptosis pathway Intrinsic Extrinsic

  6. Mild hypothermia therapy • K. Kataoka, H. Yanase, Mild hypothermia—A revived countermeasure against ischemic neuronal damages, Neurosci. Res. 32 (1998) 103– 117. • 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. • F. Shann, Hypothermia for traumatic brain injury: how soon, how cold, and how long? Lancet 362 (2003) 1950– 1951. • M.F. Hong, P. Dorian, Update on advanced life support and resuscitation techniques, Curr. Opin. Cardiol. 20 (2005) 1 – 6.

  7. Aim • Hypothermia ( 32℃ ) protects cells from apoptosis induced by a variety of stress conditions ( ER , DNA damage & Fas-mediated stresses ) • Hypothermia molecular mechanism.

  8. Effects of hypothermia on Thapsigargin-induced apoptosis ( ER stress ) Thapsigargin: An inhibitor of Endoplasmic reticulum ( ER ) Ca+2 ATPase pumps 32℃ 37℃

  9. Inhibition of topoisomerases DNA damage Osmotic stress Oxidative stress Fas-mediated 32℃ 32℃ 37℃ 37℃ Effects of hypothermia on cell death induced by various stresses

  10. Modified apoptosis pathway Intrinsic Extrinsic

  11. 32℃ 37℃ Molecular mechanism of hypothermia on Thapsigargin-induced apoptosis ( ER stress ) Protein translocation p53 -/-/ Mdm2 -/- cells Anti-apoptotic effects of hypothermia on thapsigargin-treated cells are p53-independent

  12. 32℃ 37℃ Molecular mechanism of hypothermia on Adriamycin-induced apoptosis ( DNA damage ) Bcl-xL: anti-apoptotic Bcl-2 family of protein

  13. Modified apoptosis pathway Intrinsic Extrinsic

  14. 32℃ 37℃ 37℃ 32℃ Effect of hypothermia on the level of p53 P53 transcript MG132: A proteasome inhibitor

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