Role of NF-E2-related factor 2 in neuroprotective effect of l-carnitine against high glucose-induced oxidative stress in the retinal ganglion cells

Biomed Pharmacother. 2015 Feb:69:345-8. doi: 10.1016/j.biopha.2014.12.030. Epub 2014 Dec 23.

Abstract

l-Carnitine (LC) has protective effects on high glucose-induced oxidative stress in the retinal ganglion cells (RGCs). The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2), Kelch like-ECH-associated protein 1 (Keap1), haemoxygenase-1 (HO-1) and γ-glutamyl cysteine synthetase (γ-GCS) in the protective effect of LC on RGCs. RGCs were first processed with high concentrations of glucose. LC treatment at three concentrations (50μM, 100μM and 200μM) was applied to high glucose stimulated RGCs. The expression of Nrf2, Keap1, haemoxygenase-1 (HO-1) and γ-glutamyl cysteine synthetase (γ-GCS) was quantified by Western blot in the treatment and control (high glucose stimulation) groups. In the three LC groups (50μM, 100μM and 200μM), Nrf-2 (0.71±0.04, 0.89±0.05, 1.24±0.05 vs 0.56±0.03, p<0.05), HO-1 (0.58±0.04, 0.76±0.06, 0.89±0.07 vs 0.25±0.03, p<0.01), and γ-GCS protein expression (0.66±0.03, 0.79±0.05, 0.84±0.08 vs 0.84±0.08, p<0.01) was higher than in the control group. The levels of Keap1 protein were in the LC groups were lower than in the control group (0.50±0.03, 0.45±0.02, 0.53±0.03 vs 0.86±0.05, p<0.01). In conclusion, in high glucose stimulated RGCs, LC treatment was associated with an increased level of Nrf2, HO-1and γ-GCS. LC treatment was also associated with a reduced expression of Keap1 protein. These results suggest that the protective effect of LC treatment on RGCs may be related to Nrf2-Keap1 pathway.

Keywords: Antioxidant defense; Diabetic retinopathy; Keap-1; Nrf2; l-Carnitine.

MeSH terms

  • Animals
  • Carnitine / pharmacology*
  • Cell Shape / drug effects
  • Glucose / toxicity*
  • Glutamate-Cysteine Ligase / metabolism
  • Heme Oxygenase-1
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2 / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Rats, Wistar
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / enzymology
  • Retinal Ganglion Cells / metabolism*
  • Retinal Ganglion Cells / pathology*

Substances

  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, rat
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Neuroprotective Agents
  • Heme Oxygenase-1
  • Glutamate-Cysteine Ligase
  • Glucose
  • Carnitine