Abstract
Quercetin, a polyphenolic compound existing in many vegetables, fruits, has antiinflammatory, antiproliferation, and antioxidant effect on mammalian cells. Quercetin was evaluated for protecting cardiomyocytes from ischemia/reperfusion injury, but its protective mechanism remains unclear in the current study. The cardioprotective effects of quercetin are achieved by reducing the activity of Src kinase, signal transducer and activator of transcription 3 (STAT3), caspase 9, Bax, intracellular reactive oxygen species production, and inflammatory factor and inducible MnSOD expression. Fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) can reveal the differentially expressed proteins of H9C2 cells treated with H2O2 or quercetin. Although 17 identified proteins were altered in H2O2-induced cells, these proteins such as alpha-soluble NSF attachment protein (α-SNAP), Ena/VASP-like protein (Evl), and isopentenyl-diphosphate delta-isomerase 1 (Idi-1) were reverted by pretreatment with quercetin, which correlates with kinase activation, DNA repair, lipid, and protein metabolism. Quercetin dephosphorylates Src kinase in H2O2-induced H9C2 cells and likely blocks the H2O2-induced inflammatory response through STAT3 kinase modulation. This probably contributes to prevent ischemia/reperfusion injury in cardiomyocytes.
Highlights
Because of their high incidence and mortality rate, cardiovascular diseases have recently become a primary health concern worldwide
Because heart ischemia/reperfusion injury stimulates H2O2 production, H9C2 cells were treated with varying H2O2 doses to find the optimal phosphotyrosine response
Results show that 5 mM H2O2 treatment led to a robust phosphotyrosine response, but the phosphotyrosine response decreased in 10 mM H2O2 cells
Summary
Because of their high incidence and mortality rate, cardiovascular diseases have recently become a primary health concern worldwide. Src kinase plays a key role in ROS-induced phosphorylation and cell damage in cardiomyocytes [2]. The ROS in this study includes hydrogen peroxide (H2O2), singlet oxygen (O∙), superoxide (O2−), and the hydroxyl radical (OH∙) Among these ROS species, H2O2 is the most stable and the most abundant in human cells. Several reports have shown that quercetin has protective effects on different types of cells, including myocytes, testis, renal cells, and liver cells in ischemia/reperfusion injury [5]. Quercetin has been reported to play a role in protecting myocardial cells from ischemia/reperfusion injury, its protective mechanism remains unclear in current knowledge. We focus on the correlation between quercetin in cardiomyocytes and the cardioprotective role of Src kinase inhibition and inflammatory response of STAT3 using 2D-DIGE combined with MALDITOF MS and immunoblotting
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