title: Propofol protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via Akt activation and Bcl-2 up-regulation.
abstract: Propofol is a widely used intravenous anesthetic agent with antioxidant properties secondary to its phenol based chemical structure. Treatment with propofol has been found to attenuate oxidative stress and prevent ischemia/reperfusion injury in rat heart. Here, we report that propofol protects cardiac H9c2 cells from hydrogen peroxide (H(2)O(2))-induced injury by triggering the activation of Akt and a parallel up-regulation of Bcl-2. We show that pretreatment with propofol significantly protects against H(2)O(2)-induced injury. We further demonstrate that propofol activates the PI3K-Akt signaling pathway. The protective effect of propofol on H(2)O(2)-induced injury is reversed by PI3K inhibitor wortmannin, which effectively suppresses propofol-induced activation of Akt, up-regulation of Bcl-2, and protection from apoptosis. Collectively, our results reveal a new mechanism by which propofol inhibits H(2)O(2)-induced injury in cardiac H9c2 cells, supporting a potential application of propofol as a preemptive cardioprotectant in clinical settings such as coronary bypass surgery.
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada V5Z 4E3.
authors.forename: Baohua
authors.initials: B
authors.lastname: Wang
authors.forename: Jayant
authors.initials: J
authors.lastname: Shravah
authors.forename: Honglin
authors.initials: H
authors.lastname: Luo
authors.forename: Koen
authors.initials: K
authors.lastname: Raedschelders
authors.forename: David D Y
authors.initials: DD
authors.lastname: Chen
authors.forename: David M
authors.initials: DM
authors.lastname: Ansley
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D001026:Coronary Artery Bypass / Q000009:adverse effects; D019610:Cytoprotection; D006861:Hydrogen Peroxide / Q000633:toxicity; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018686:Anesthetics, Intravenous; D000975:Antioxidants; D002316:Cardiotonic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; D015742:Propofol
references.citation: Heart Fail Rev. 2007 Dec;12(3-4):217-34
references.pmid: 17541822
references.citation: Circ Res. 1991 Dec;69(6):1476-86
references.pmid: 1683272
references.citation: J Clin Invest. 2005 Oct;115(10):2618-24
references.pmid: 16200194
references.citation: Br J Anaesth. 2006 Dec;97(6):825-31
references.pmid: 17032661
references.citation: Cardiovasc Res. 2003 Jul 1;59(1):113-21
references.pmid: 12829182
references.citation: Anesthesiology. 2002 Dec;97(6):1557-66
references.pmid: 12459685
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Can J Physiol Pharmacol. 2003 Jan;81(1):14-21
references.pmid: 12665253
references.citation: Am J Chin Med. 2006;34(4):695-706
references.pmid: 16883639
references.citation: J Biol Chem. 2006 Jun 16;281(24):16473-81
references.pmid: 16613850
references.citation: Anesth Analg. 2005 Jun;100(6):1653-1659
references.pmid: 15920191
references.citation: J Mol Cell Cardiol. 2005 Jan;38(1):63-71
references.pmid: 15623422
references.citation: J Clin Immunol. 2005 Nov;25(6):541-50
references.pmid: 16380818
references.citation: Circulation. 2001 Jul 17;104(3):253-6
references.pmid: 11457740
references.citation: Circulation. 2001 Jan 30;103(4):555-61
references.pmid: 11157722
references.citation: Anesthesiology. 2006 May;104(5):978-87
references.pmid: 16645450
references.citation: Can J Anaesth. 1998 Mar;45(3):233-9
references.pmid: 9579261
references.citation: Pharmacol Ther. 2008 Nov;120(2):172-85
references.pmid: 18786563
references.citation: Anesth Analg. 2007 Oct;105(4):1027-33, table of contents
references.pmid: 17898383
references.citation: Cardiovasc Res. 2000 Jan 14;45(2):360-9
references.pmid: 10728356
references.citation: J Mol Cell Cardiol. 2007 Nov;43(5):580-92
references.pmid: 17920074
references.citation: Circulation. 1999 Nov 9;100(19 Suppl):II369-75
references.pmid: 10567332
references.citation: J Mol Cell Cardiol. 2009 May;46(5):607-9
references.pmid: 19318238
references.citation: Can J Anaesth. 2009 Sep;56(9):658-66
references.pmid: 19639375
references.citation: Eur J Anaesthesiol. 2008 May;25(5):395-402
references.pmid: 18289444
references.citation: Anesthesiology. 1996 Jan;84(1):117-27
references.pmid: 8572324