Melatonin protects against oxidative stress in granular corneal dystrophy type 2 corneal fibroblasts by mechanisms that involve membrane melatonin receptors.

Abstract

Considering that oxidative stress plays a role in corneal fibroblast degeneration during granular corneal dystrophy type 2 (GCD2) and melatonin is an effective antioxidant, we examined the ability of melatonin to protect against oxidative stress-induced cell death of primary cultured normal and GCD2-homozygous corneal fibroblasts. Melatonin treatment protected primary cultured normal and GCD2 corneal fibroblasts from paraquat (PQ)-induced oxidative stress and caused increased expression levels of Cu/Zn-superoxide dismutase (SOD1) and glutathione reductase (GR) in both types of cells. Interestingly, catalase expression increased in normal corneal fibroblasts, but decreased in GCD2 corneal fibroblasts after melatonin treatment. Melatonin also reduced the levels of intracellular reactive oxygen species and H(2)O(2) in both cell types. In addition, the selective melatonin receptor antagonist luzindole blocked melatonin-induced expression of SOD1 and GR. The expression levels of melatonin receptors 1A (MT1) and 1B (MT2) were significantly higher in GCD2 corneal fibroblasts than in normal cells. These results suggest that increased expression of melatonin receptors may be involved in the defense mechanisms against oxidative stress in GCD2 corneal fibroblasts, and melatonin may have potential therapeutic implications for GCD2 treatment.

• Authors: Seung-Il Choi, Shorafidinkhuja Dadakhujaev, Hyunmi Ryu, Tae Im Kim, Eung Kweon Kim
• Journal: Journal of pineal research (J Pineal Res) Vol. 51 Issue 1 Pg. 94-103 (Aug 2011) ISSN: 1600-079X [Electronic] England
• PMID: 21392093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Antioxidants
• Reactive Oxygen Species
• Receptors, Melatonin
• Hydrogen Peroxide
• Catalase
• Superoxide Dismutase
• Glutathione Reductase
• Melatonin
• Paraquat

Topics

• Analysis of Variance
• Antioxidants (pharmacology)
• Blotting, Western
• Catalase (metabolism)
• Cell Survival (drug effects)
• Cells, Cultured
• Cornea (drug effects, pathology)
• Corneal Dystrophies, Hereditary (drug therapy, metabolism, pathology)
• Fibroblasts (drug effects, metabolism, pathology)
• Flow Cytometry
• Glutathione Reductase (metabolism)
• Humans
• Hydrogen Peroxide (metabolism)
• Immunohistochemistry
• Melatonin (pharmacology)
• Oxidative Stress (drug effects)
• Paraquat (pharmacology)
• Reactive Oxygen Species (metabolism)
• Receptors, Melatonin (metabolism)
• Superoxide Dismutase (metabolism)