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

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 gamma-glutamyl cysteine synthetase (gamma-GCS) in the protective effect of LC on RGCs. RGCs were first processed with high concentrations of glucose. LC treatment at three concentrations (50 mu M, 100 mu M and 200 mu M) was applied to high glucose stimulated RGCs. The expression of Nrf2, Keap1, haemoxygenase-1 (HO-1) and gamma-glutamyl cysteine synthetase (gamma-GCS) was quantified by Western blot in the treatment and control (high glucose stimulation) groups. In the three LC groups (50 mu M, 100 mu M and 200 mu M), 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 gamma-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 gamma-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. (C) 2015 Elsevier Masson SAS. All rights reserved.