title: Sulforaphane inhibits advanced glycation end product-induced pericyte damage by reducing expression of receptor for advanced glycation end products.
abstract: Advanced glycation end products (AGEs) not only inhibit DNA synthesis but also play a role in diabetic retinopathy by evoking apoptosis and inflammation in retinal pericytes via interaction with a receptor for AGE (RAGE). Similarly, sulforaphane, which is a naturally occurring isothiocyanate that is found in widely consumed cruciferous vegetables, protects against oxidative stress-induced tissue damage. Therefore, we hypothesized that sulforaphane could inhibit AGE-induced pericytes injury through its antioxidative properties. Advanced glycation end product stimulated superoxide generation as well as RAGE gene and protein expression in bovine-cultured retinal pericytes, and these effects were prevented by the treatment with sulforaphane. Antibodies directed against RAGE also blocked AGE-evoked reactive oxygen species generation in pericytes. Sulforaphane and antibodies directed against RAGE significantly inhibited the AGE-induced decrease in DNA synthesis, apoptotic cell death, and up-regulation of monocyte chemoattractant protein 1 messenger RNA levels in pericytes. For the first time, the present study demonstrates that sulforaphane could inhibit DNA synthesis, apoptotic cell death, and inflammatory reactions in AGE-exposed pericytes, partly by suppressing RAGE expression via its antioxidative properties. Blockade of the AGE-RAGE axis in pericytes by sulforaphane might be a novel therapeutic target for the treatment of diabetic retinopathy.
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ojima
authors.affiliation: Department of Advanced Medicine Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. Electronic address: shoichi@med.kurume-u.ac.jp.
authors.forename: Sho-Ichi
authors.initials: S
authors.lastname: Yamagishi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019607:Brassicaceae / Q000737:chemistry*; D002417:Cattle; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007249:Inflammation / Q000517:prevention & control; D017879:Isothiocyanates / Q000494:pharmacology* / Q000627:therapeutic use; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013454:Sulfoxides; D013481:Superoxides / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D017879:Isothiocyanates; D010936:Plant Extracts; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013454:Sulfoxides; D013481:Superoxides; D004247:DNA; C016766:sulforaphane
keywords: AGE; Diabetic retinopathy; Oxidative stress; Pericytes; RAGE; Sulforaphane