title: Cardioprotective effects of monocyte locomotion inhibitory factor on myocardial ischemic injury by targeting vimentin.
abstract: Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide produced by Entamoeba histolytica, has anti-inflammatory function and protective effect on ischemic stroke. In this study, we evaluated the effect of MLIF on myocardial ischemia. Mice were subjected to ischemia/reperfusion by occlusion of the left anterior descending artery (LAD). After sacrifice, the serum concentrations of cardiac troponin I (cTnI), creatine kinase (CK), lactate dehydrogenase (LDH) as well as the heart infarct size were measured. HE and TUNEL staining were used to observe the pathological damage and the apoptotic cells. For in vitro study, the oxygen-glucose deprivation(OGD) model was established in H9c2 cells. MTT assay and flow cytometry assay were performed to evaluate cell viability and apoptosis. The expression of JNK and caspase 3 was assessed by western blot analysis. Pull-down assay was used to detect the specific binding protein of MLIF in myocardial cells. MLIF significantly reduced the infarct size, and the cTnI, CK and LDH levels, amelioratived pathological damage and reduced the apopotosis compared with the myocardial I/R model group. MLIF improved cell survival and inhibited apoptosis and necrosis by inhibiting the p-JNK and cleaved caspase3 expression. Furthermore, the binding protein of MLIF in myocardial cells was vimentin. Inhibition of vimentin expression by withaferin A or vimentin siRNA repressed the protective effects of MLIF in OGD-provoked H9c2 cells. Taken together, our results demonstrate that the cardioprotective effects of MLIF on myocardial ischemia injury are related to reductions in the inflammatory response and apoptosis by targeting vimentin.
authors: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai, PR China; Department of Pharmacy, Punan Hospital, Pudong New District, Shanghai, PR China.
authors: Shu
authors: S
authors: Jiang
authors: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai, PR China.
authors: Yulan
authors: Y
authors: Liu
authors: College of Pharmacology, Anhui University of Chinese Medicine, Hefei, Anhui, PR China.
authors: Jing
authors: J
authors: Wang
authors: College of Pharmacology, Anhui University of Chinese Medicine, Hefei, Anhui, PR China.
authors: Yue
authors: Y
authors: Zhang
authors: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai, PR China.
authors: Yaocheng
authors: Y
authors: Rui
authors: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai, PR China. Electronic address: zhangyuefan@126.com.
authors: Yuefan
authors: Y
authors: Zhang
authors: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai, PR China; Department of Pharmacy, Punan Hospital, Pudong New District, Shanghai, PR China. Electronic address: ltj204@163.com.
authors: Tiejun
authors: T
authors: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D003402:Creatine Kinase / Q000097:blood; D004748:Entamoeba histolytica / Q000737:chemistry; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000627:therapeutic use*; D019210:Troponin I / Q000097:blood; D014746:Vimentin / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D002316:Cardiotonic Agents; D009842:Oligopeptides; D019210:Troponin I; D014746:Vimentin; C430647:monocyte locomotion inhibitory factor; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase
keywords: Acute myocardial ischemic injury; Apoptosis; Monocyte locomotion inhibitory factor; Vimentin