Dataset Information

Osmotin Protects H9c2 Cells from Simulated Ischemia-Reperfusion Injury through AdipoR1/PI3K/AKT Signaling Pathway.

ABSTRACT: Objective: This study aimed to investigate the effect of osmotin on myocardial ischemia/reperfusion (I/R), as well as the underlying mechanisms. Methods:In vitro I/R injury model was established on rat cardiac myoblast H9c2 cells by oxygen and glucose deprivation followed by reperfusion (OGD/R). Cells were administrated with osmotin, and transfected with small interfering RNAs (siRNAs) which specifically target adiponectin receptor 1 or 2 (AdipoR1/2). Besides, the cells were incubated with or without LY294002 as inhibitor of phosphatidylinositol 3-kinase (PI3K) under OGD/R condition. Cell viability, apoptosis, expressions of apoptosis-related proteins and inflammatory factors were analyzed. Results: The results showed that osmotin significantly increased H9c2 cells viability compared with the cells treated with vehicle (P < 0.05), and decreased H9c2 cells apoptosis by regulating expressions of apoptosis-related proteins. Moreover, we observed that osmotin statistically reduced the release of proinflammatory factors and increased the release of anti-inflammatory factors in H9c2 cells (P < 0.05). However, these effects were markedly reversed by AdipoR1 silence but not AdipoR2. Furthermore, osmotin dramatically upregulated the phosphorylation levels of PI3K, AKT, ERK, and downregulated the phosphorylation level of NF-?B (P < 0.05). While administration of LY294002 reduced cell viability, increased cell apoptosis, and aggravated inflammatory response (P < 0.05). Conclusion: Our results suggested that the protective effect of osmotin on the simulated OGD/R injured H9c2 cells might be associated with AdipoR1/PI3K/AKT signaling pathway.

SUBMITTER: Liu J

PROVIDER: S-EPMC5622187 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Osmotin Protects H9c2 Cells from Simulated Ischemia-Reperfusion Injury through AdipoR1/PI3K/AKT Signaling Pathway.

Liu Jianhua J Sui Hua H Zhao Jianlin J Wang Yan Y

Frontiers in physiology 20170925

Objective: This study aimed to investigate the effect of osmotin on myocardial ischemia/reperfusion (I/R), as well as the underlying mechanisms. Methods:In vitro I/R injury model was established on rat cardiac myoblast H9c2 cells by oxygen and glucose deprivation followed by reperfusion (OGD/R). Cells were administrated with osmotin, and transfected with small interfering RNAs (siRNAs) which specifically target adiponectin receptor 1 or 2 (AdipoR1/2). Besides, the cells were ...[more]

PMID: 28993734

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Project description:Search for new cardioprotective therapies is of great importance since no cardioprotective drugs are available on the market. In line with this need, several natural biomolecules have been extensively tested for their potential cardioprotective effects. Previously, we have shown that biglycan, a member of a diverse group of small leucine-rich proteoglycans, enhanced the expression of cardioprotective genes and decreased ischemia/reperfusion-induced cardiomyocyte death via a TLR-4 dependent mechanism. Therefore, in the present study we aimed to test whether decorin, a small leucine-rich proteoglycan closely related to biglycan, could exert cardiocytoprotection and to reveal possible downstream signaling pathways. Methods: Primary cardiomyocytes isolated from neonatal and adult rat hearts were treated with 0 (Vehicle), 1, 3, 10, 30 and 100 nM decorin as 20 h pretreatment and maintained throughout simulated ischemia and reperfusion (SI/R). In separate experiments, to test the mechanism of decorin-induced cardio protection, 3 nM decorin was applied in combination with inhibitors of known survival pathways, that is, the NOS inhibitor L-NAME, the PKG inhibitor KT-5823 and the TLR-4 inhibitor TAK-242, respectively. mRNA expression changes were measured after SI/R injury. Results: Cell viability of both neonatal and adult cardiomyocytes was significantly decreased due to SI/R injury. Decorin at 1, 3 and 10 nM concentrations significantly increased the survival of both neonatal and adult myocytes after SI/R. At 3nM (the most pronounced protective concentration), it had no effect on apoptotic rate of neonatal cardiac myocytes. No one of the inhibitors of survival pathways (L-NAME, KT-5823, TAK-242) influenced the cardiocytoprotective effect of decorin. MYND-type containing 19 (Zmynd19) and eukaryotic translation initiation factor 4E nuclear import factor 1 (Eif4enif1) were significantly upregulated due to the decorin treatment. In conclusion, this is the first demonstration that decorin exerts a direct cardiocytoprotective effect possibly independent of NO-cGMP-PKG and TLR-4 dependent survival signaling.

Project description:BackgroundIschemia stroke is the leading cause of disability, which is a consequence of vascular occlusion. The purpose of this study is to investigate the effect of cornin which is isolated from the fruit of Verbena officinalis L, against astrocytes autophagy induced by cerebral ischemia/reperfusion (CI/R) injury in vitro and in vivo and its potential mechanism.MethodsCornin at dose of 2.5, 5 and 10 mg/kg were intravenously injected to MCAO rats at 15 min after reperfusion. The infarction volume, blood-brain barrier (BBB), neurological severity score (mNSS), and autophagy related protein were used to evaluated the protective effects and potential mechanism of cornin in autophagy with or without phosphoinositide-3 kinase (PI3K)inhibitor LY294002 and mammalian target of rapamycin (mTOR) small interfering RNA (siRNA) at 24 h after CI/R injury. The potential protective effects and mechanism of cornin at concention of 10 ~ 1000 nM were also evaluated in oxygen glucose deprivation/reperfusion (OGD/R) in U87 cells.ResultsThe results suggest that cornin at dose of 5 or 10 mg/kg significantly reduce the cerebral infarction volume and blood-brain barrier (BBB) leakage, and improve neurological recovery in MCAO rats. Cleaved caspase-3 and Bax levels were significantly decreased, while B-cell lymphoma-2 (Bcl-2) and the apoptosis regulator ratio (Bcl-2/Bax) were markedly increased when treated with 2.5-10 mg/kg cornin. The obvious decreased expressions of glial fibrillary acidic protein (GFAP), myosin-like BCL2 interacting protein (Beclin-1) and microtubule-associated protein light chain 3 II (LC3-II) and increased of neuronal nuclei (NeuN), sequestosome-1 (p62), phosphorylated mTOR (p-mTOR), and phosphorylated Akt (p-Akt) were observed in MCAO rats treated with 10 mg/kg cornin, which was counteracted by LY294002. The expression of autophagy-related proteins with or without LY294002 and mTOR siRNA presented the similar results as in vitro in OGD/R in U87 cells.ConclusionsThese results indicate that cornin improved neurological recovery after cerebral ischemia injury by preventing astrocytes autophagy induced by CI/R via the PI3K/Akt/mTOR signaling pathway.

Dataset Information

Osmotin Protects H9c2 Cells from Simulated Ischemia-Reperfusion Injury through AdipoR1/PI3K/AKT Signaling Pathway.

Publications

Osmotin Protects H9c2 Cells from Simulated Ischemia-Reperfusion Injury through AdipoR1/PI3K/AKT Signaling Pathway.

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