Authors: Tao Chen Guoliang Ding Zhuqing Jin Mary B Wagner Zuyi Yuan
Publish Date: 2012/07/18
Volume: 369, Issue: 1-2, Pages: 167-174
Abstract
Growing evidence indicates that aberrant upregulation of microRNA1 miR1 occurs in ischemic myocardium In addition insulin elicits metabolismindependent cardioprotection against cardiovascular diseases The aim of this study is to determine whether insulin ameliorates miR1induced injury in H9c2 cells under oxidative stress and to investigate the underlying mechanisms By quantitative realtime RTPCR qRTPCR we show that miR1 is upregulated in H9c2 cells after treatment with hydrogen peroxide H2O2 and this effect is both dose and time dependent Furthermore expression of miR1 decreased significantly after insulin treatment 45 ± 01 vs 30 ± 02 p 005 To determine the potential role of miR1 in cellular injury and gene regulation adenovirusmediated overexpression of miR1 was used Overexpression of miR1 decreased cell viability by 28 ± 2 n = 6 p 005 and damaged Akt activation with or without H2O2 treatment To further investigate the effect of the phosphatidylinositol 3kinase PI3K/Akt pathway in miR1induced injury H9c2 cells were pretreated with LY294002 10 μM LY a specific inhibitor of PI3K with or without insulin 100 nM and subjected to H2O2 treatment LY pretreatmentinhibited Akt activation lead to increased reactive oxygen species ROS and further decreased cell viability induced by miR1 n = 6 p 005 n = 9–10 cells/group p 005 and n = 6 p 005 under oxidative stress This effect was abolished by insulin In summary our findings suggest that miR1expression is sensitive to H2O2 stimulation In addition insulin decreases miR1 expression and induces a marked protective effect on miR1induced injury under oxidative stress which may be mediated by the Aktmediated pathway These results provide an important novel clue as to the mechanism of the cardiovascular action of insulin
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