Zeaxanthin ameliorates high glucose-induced mesangial cell apoptosis through inhibiting oxidative stress via activating AKT signalling-pathway

Biomed Pharmacother. 2017 Jun:90:796-805. doi: 10.1016/j.biopha.2017.04.013. Epub 2017 Apr 18.

Abstract

Oxidative stress is a critical factor in the pathophysiology of diabetic kidney disease. Previous study shows that hyperglycaemia aggravates renal injury through oxidative stress in diabetic model, and antioxidants have beneficial effect on diabetic kidney disease. However, the role of antioxidants in the progression of diabetic kidney disease is poorly understood. The aim of this study was to clarify whether zeaxanthin, an antioxidant, could ameliorate mesangial cell injury and if so, identify the related mechanism underlying this protective effect. To that end, superoxide dismutase (SOD) activity and methane dicarboxylic aldehyde (MDA) levels were measured by an assay kit, and mesangial cell apoptosis and ROS levels were assessed using flow cytometry analysis. Furthermore, The levels of a phosphorylated ser/thr protein kinase (p-AKT), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β), Bcl-2 associated X protein (Bax) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were detected by western blot. We found that zeaxanthin decreases MDA levels and increased SOD activity, as well as inhibits apoptosis and decreases ROS levels in mesangial cells in a high sugar environment. Furthermore, zeaxanthin increased p-AKT levels while decreased the levels of p-GSK-3β, Bax and cleaved-caspase-3. In addition, LY294002 reversed the protective effect of zeaxanthin on mesangial cells. In conclusion, zeaxanthin ameliorated mesangial cell apoptosis may be involved in inhibiting oxidative stress through activating of the AKT signalling pathway.

Keywords: Cleaved-caspase-3; Glomerular mesangial cells; Zeaxanthin; p-AKT.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Chromones / pharmacology
  • Glucose / metabolism*
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Mesangial Cells / drug effects*
  • Mesangial Cells / metabolism
  • Morpholines / pharmacology
  • Oxidative Stress / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Zeaxanthins / pharmacology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Chromones
  • Morpholines
  • Reactive Oxygen Species
  • Zeaxanthins
  • bcl-2-Associated X Protein
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Phosphatidylinositol 3-Kinases
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Caspase 3
  • Glucose