Contribution of the PI 3-kinase/Akt survival pathway toward osmotic preconditioning

Viktor Pastukh, Craig Ricci, Viktoriya Solodushko, Mahmood S Mozaffari, Stephen W. Schaffer

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Osmolytes are rapidly lost from the ischemic heart, an effect thought to benefit the heart by reducing the osmotic load. However, the observation that chronic lowering of one of the prominent osmolytes, taurine, is more beneficial to the ischemic heart than acute taurine loss suggests that osmotic stress may benefit the ischemic heart through multiple mechanisms. The present study examines the possibility that chronic osmotic stress preconditions the heart in part by stimulating a cardioprotective, osmotic-linked signaling pathway. Hyperosmotic stress was produced by treating rat neonatal cardiomyocytes during the pre-hypoxic period with either the taurine depleting agent, ß-alanine (5 mM), or with medium containing 25 mM mannitol. The cells were then subjected to chemical hypoxia in medium containing 3 mM Amytal and 10 mM deoxyglucose but lacking ß-alanine and mannitol. Cells that had been pretreated with either 5 mM ß-alanine or 25 mM mannitol exhibited resistance gainst hypoxia-induced apoptosis and necrosis. Associated with the osmotically preconditioned state was the activation of Akt and the inactivation of the pro-apoptotic factor, Bad, both events blocked by the inhibition of PI 3-kinase. However, preconditioning the cardiomyocyte with mannitol had no effect on the generation of free radicals during the hypoxic period. Osmotic stress also promoted the upregulation of the anti-apoptotic factor, Bcl-2. Since inhibition of PI 3-kinase with Wortmannin also prevents osmotic-mediated cardioprotection, we conclude that hyperosmotic-mediated activation of the PI 3-kinase/Akt pathway contributes to osmotic preconditioning.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume269
Issue number1
DOIs
StatePublished - Jan 1 2005

Fingerprint

Phosphatidylinositol 3-Kinases
Mannitol
Taurine
Osmotic Pressure
Alanine
Cardiac Myocytes
Chemical activation
Amobarbital
Cohort Effect
Deoxyglucose
Free Radicals
Rats
Necrosis
Up-Regulation
Apoptosis
Hypoxia

Keywords

  • Akt
  • Apoptosis
  • Bcl-2 family
  • Hypoxia
  • Osmotic stress
  • Preconditioning
  • Taurine

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Contribution of the PI 3-kinase/Akt survival pathway toward osmotic preconditioning. / Pastukh, Viktor; Ricci, Craig; Solodushko, Viktoriya; Mozaffari, Mahmood S; Schaffer, Stephen W.

In: Molecular and Cellular Biochemistry, Vol. 269, No. 1, 01.01.2005, p. 59-67.

Research output: Contribution to journalArticle

Pastukh, Viktor ; Ricci, Craig ; Solodushko, Viktoriya ; Mozaffari, Mahmood S ; Schaffer, Stephen W. / Contribution of the PI 3-kinase/Akt survival pathway toward osmotic preconditioning. In: Molecular and Cellular Biochemistry. 2005 ; Vol. 269, No. 1. pp. 59-67.
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