Erythropoietin prevents reactive oxygen species generation and renal tubular cell apoptosis at high glucose level

Biomed Pharmacother. 2010 Dec;64(10):681-5. doi: 10.1016/j.biopha.2010.06.011. Epub 2010 Jul 16.

Abstract

Erythropoietin (EPO) can induce a series of cytoprotective effects in many non-hematopoietic tissues through interaction with the erythropoietin receptor (EPOR), but whether EPO can prevent the overproduction of reactive oxygen species (ROS) and apoptosis in diabetes remains unclear. Here, we report that renal tubular cells possess EPOR and that EPO reduces high glucose-induced oxidative stress in renal tubular cells. Further, we found that EPO inhibited high glucose-induced renal tubular cell apoptosis and that this protective effect was dependent on reduction of Bax/caspase-3 expression as well as elevation of Bcl-2 expression. Our results suggest that EPO can inhibit high glucose-induced renal tubular cell apoptosis through direct effect on anti-oxidative stress and that EPOR may play a key role in this process.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / biosynthesis
  • Caspase 3 / genetics
  • Caspase Inhibitors
  • Cell Line
  • Erythropoietin / pharmacology*
  • Flow Cytometry
  • Glucose / administration & dosage*
  • Glucose / metabolism
  • Kidney Tubular Necrosis, Acute / metabolism
  • Kidney Tubular Necrosis, Acute / pathology
  • Kidney Tubules / cytology
  • Kidney Tubules / drug effects*
  • Kidney Tubules / metabolism
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Receptors, Erythropoietin / biosynthesis
  • Receptors, Erythropoietin / genetics
  • Receptors, Erythropoietin / metabolism
  • bcl-2-Associated X Protein / antagonists & inhibitors
  • bcl-2-Associated X Protein / biosynthesis
  • bcl-2-Associated X Protein / genetics

Substances

  • Bax protein, rat
  • Caspase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Reactive Oxygen Species
  • Receptors, Erythropoietin
  • bcl-2-Associated X Protein
  • Erythropoietin
  • Caspase 3
  • Glucose