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Regulation of Cannabinoid‐mediated Neuroprotection by Hydrogen Sulfide in Bovine Isolated Retina
Author(s) -
Mitchell Leah,
Robinson Jenaye,
Ngele Kalu,
Opere Catherine,
Ohia Sunny E,
NjieMbye Ya Fatou
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb602
Subject(s) - am251 , neuroprotection , cannabinoid receptor , endocannabinoid system , chemistry , cannabinoid , pharmacology , biochemistry , oxidative stress , lipid peroxidation , anandamide , antagonist , receptor , biology
Hydrogen sulfide (H 2 S) and endocannabinoids have been reported to possess neuroprotective properties in several mammalian tissues. In the present study, we will investigate the role of H 2 S in the neuroprotective actions of cannabinoids in the bovine isolated neural retina. Methods Isolated bovine retinae were exposed to oxidative stress using hydrogen peroxide (H 2 O 2 , 100 μM) for 10 minutes. Before exposure to stress, tissues were pretreated with inhibitors of H 2 S biosynthesis, amino‐oxyacetic acid (AOAA, 30 μM) and α‐keto‐butyric acid (KBA, 1 mM), and the CB1‐receptor antagonist, AM251 (100 nM) prior to treatment with methanandamide (1 nM – 100 nM). Lipid peroxidation was assessed using the Cayman 8‐isoprostane ELISA kit. Results In the presence of H 2 O 2 (100 μM), there was a 20% increase in 8‐isoprostane levels when compared to control. At a concentration of 1 nM, methanandamide significantly (P<0.001) reversed the H 2 O 2 (100 μM)‐induced augmentation in 8‐isoprostane levels in the neural retina. Interestingly, the neuroprotective action caused by methanandamide was abolished by KBA (1 mM) but not by AM251 (100 nM) or AOAA (30 μM). Conclusions Our results demonstrate that the neuroprotective action of methanadamide can be reversed by an inhibitor of the enzyme, 3‐mercaptopyruvate sulfurtransferase but not by the CB1‐receptor antagonist. Taken together, we conclude that the neuroprotective action of endocannabinoids involve the endogenous biosynthesis of H 2 S via the cysteine aminotransferase dependent pathway in the bovine retina.