title: Leptin suppresses non-apoptotic cell death in ischemic rat cardiomyocytes by reduction of iPLA(2) activity.
abstract: Caspase-independent, non-apoptotic cell death is an important therapeutic target in myocardial ischemia. Leptin, an adipose-derived hormone, is known to exhibit cytoprotective effects on the ischemic heart, but the mechanisms are poorly understood. In this research, we found that pretreatment of leptin strongly suppressed ischemic-augmented nuclear shrinkage and non-apoptotic cell death on cardiomyocytes. Leptin was also shown to significantly inhibit the activity of iPLA2, which is considered to play crucial roles in non-apoptotic cell death, resulting in effective prevention of ischemia-induced myocyte death. These findings provide the first evidence of a protective mechanism of leptin against ischemia-induced non-apoptotic cardiomyocyte death.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan. Electronic address: nakase@mukogawa-u.ac.jp.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Takatani-Nakase
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan. Electronic address: koichi@mukogawa-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005947:Glucose / Q000008:administration & dosage; D054522:Group VI Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats
chemical_list: D016895:Culture Media, Serum-Free; D020738:Leptin; D054522:Group VI Phospholipases A2; C535117:Pla2g6 protein, rat; D005947:Glucose
keywords: Caspase-independence; Ischemia; Leptin; Non-apoptotic cell death; iPLA(2)