HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Upregulation of cytochrome P450 2J3/11,12-epoxyeicosatrienoic acid inhibits apoptosis in neonatal rat cardiomyocytes by a caspase-dependent pathway.

Abstract
Short, nonlethal ischemic episodes administered to hearts directly after ischemic events (ischemic postconditioning, IPost) have an advantage over ischemic preconditioning (IPC). The endogenous cytochrome P450 2J3/11,12-epoxyeicosatrienoic acid (CYP2J3/11,12-EET) is upregulated by IPost, but not IPC, in the rat heart. The CYP epoxygenase inhibitor N-methylsulphonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH) reduces the cardioprotective effects of IPost, but not IPC. We proposed that upregulation of CYP2J3/11,12-EET during IPost induces cardioprotection by inhibiting cardiomyocyte apoptosis and that multiple apoptotic signals, including changes in mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) opening, mitochondrial cytochrome c leakage, caspase-3 levels, and levels of protective kinases such as Bcl-2 and Bax, are involved in the process. Neonatal rat cardiomyocytes underwent 3-h hypoxia followed by 2-, 5-, or 6-h reoxygenation (H/R) or three cycles of 5-min reoxygenation followed by 5-min hypoxia before 90-min reoxygenation (HPost); or were transfected with pcDNA3.1-CYP2J3 for 48 h before H/R; or were treated with MS-PPOH for 10 min before HPost. For HPost alone, pcDNA3.1-CYP2J3 transfection attenuated cardiomyocyte apoptosis to 68.4% (p<0.05) of that with H/R. pcDNA3.1-CYP2J3 transfection significantly decreased MMP and inhibited mPTP opening induced by H/R, reduced mitochondrial cytochrome c leakage, cleaved caspase-3 protein expression, and increased the ratio of Bcl-2 to Bax expression. MS-PPOH abolished this effect. Therefore, upregulation of CYP2J3/11,12-EET during HPost is involved in cardioprotection by inhibiting apoptosis via a caspase-dependent pathway, and the apoptosis-suppressive effect may have important clinical implications during HPost.
AuthorsHong-Xia Wang, Dong-Mei Zhang, Xiang-Jun Zeng, Jing Mu, Hui Yang, Ling-Qiao Lu, Li-Ke Zhang
JournalCytokine (Cytokine) Vol. 60 Issue 2 Pg. 360-8 (Nov 2012) ISSN: 1096-0023 [Electronic] England
PMID22717287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012. Published by Elsevier Ltd.
Chemical References
  • Amides
  • Cytochrome P-450 Enzyme Inhibitors
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide
  • bcl-2-Associated X Protein
  • 11,12-epoxy-5,8,14-eicosatrienoic acid
  • Cytochromes c
  • Cytochrome P-450 Enzyme System
  • Cyp2j3 protein, rat
  • Caspase 3
  • 8,11,14-Eicosatrienoic Acid
  • Oxygen
Topics
  • 8,11,14-Eicosatrienoic Acid (analogs & derivatives, metabolism)
  • Amides (pharmacology)
  • Animals
  • Animals, Newborn
  • Apoptosis (drug effects)
  • Caspase 3 (metabolism)
  • Cell Survival (drug effects)
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System (metabolism)
  • Cytochromes c (metabolism)
  • Hypoxia (enzymology, pathology)
  • Membrane Potential, Mitochondrial (drug effects)
  • Mitochondrial Membrane Transport Proteins (metabolism)
  • Mitochondrial Permeability Transition Pore
  • Myocytes, Cardiac (drug effects, enzymology, pathology)
  • Oxygen (metabolism)
  • Rats
  • Rats, Wistar
  • Up-Regulation (drug effects)
  • bcl-2-Associated X Protein (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: