title: Role of NF-E2-related factor 2 in neuroprotective effect of l-carnitine against high glucose-induced oxidative stress in the retinal ganglion cells.
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.
authors: The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors: Yu
authors: Y
authors: Cao
authors: The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors: Xin
authors: X
authors: Li
authors: The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors: Chen-Jing
authors: CJ
authors: Wang
authors: The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors: Ping
authors: P
authors: Li
authors: The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors: Bo
authors: B
authors: Yang
authors: Department of Pharmacology, Medical College, Qingdao University, Qingdao 266071, China. Electronic address: cbwang666@126.com.
authors: Chun-Bo
authors: CB
authors: Wang
authors: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia. Electronic address: lwang@csu.edu.au.
authors: Le-Xin
authors: LX
authors: Wang
mesh_terms: D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D048430:Cell Shape / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D051547:Heme Oxygenase-1; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase; D005947:Glucose; D002331:Carnitine
keywords: Antioxidant defense; Diabetic retinopathy; Keap-1; Nrf2; l-Carnitine