1. Exendin-4 induces extracellular-superoxide dismutase through histone H3 acetylation in human retinal endothelial cells
- Author
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Yoshinori Itoh, Tetsuro Kamiya, Tetsuya Suwa, Hiroyuki Yasuda, Hirokazu Hara, Tetsuo Adachi, Atsuko Ohashi, Jun Takeda, and Shohei Nishida
- Subjects
0301 basic medicine ,Agonist ,endocrine system ,medicine.medical_specialty ,extracellular-superoxide dismutase ,SOD3 ,medicine.drug_class ,Clinical Biochemistry ,Medicine (miscellaneous) ,Incretin ,Pharmacology ,Biology ,medicine.disease_cause ,03 medical and health sciences ,Internal medicine ,exendin-4 ,medicine ,Epigenetics ,Receptor ,Histone H3 acetylation ,Nutrition and Dietetics ,epigenetics ,digestive, oral, and skin physiology ,diabetic retinopathy ,030104 developmental biology ,Endocrinology ,Original Article ,Dismutase ,incretin-based therapy ,hormones, hormone substitutes, and hormone antagonists ,Oxidative stress - Abstract
Extracellular-superoxide dismutase (genetic name SOD3) is a secreted anti-oxidative enzyme, and its presence in vascular walls may play an important role in protecting the vascular system against oxidative stress. Oxidative stress has been implicated in the pathogenesis of diabetic retinopathy; therefore, increases in extracellular-superoxide dismutase have been suggested to inhibit the progression of diabetic retinopathy. Incretin-based drugs such as glucagon-like peptide-1 receptor agonists are used in the treatment of type 2 diabetes. Glucagon-like peptide-1 receptor agonists are expected to function as extrapancreatic agents because the glucagon-like peptide-1 receptor is expressed not only in pancreatic tissues, but also in many other tissue types. We herein demonstrated that exendin-4, a glucagon-like peptide-1 receptor agonist, induced the expression of extracellular-superoxide dismutase in human retinal microvascular endothelial cells through epigenetic regulation. The results of the present study demonstrated that exendin-4 induced the expression of extracellular-superoxide dismutase through histone H3 acetylation at the SOD3 proximal promoter region. Moreover, plasma extracellular-superoxide dismutase concentrations in diabetic patients were elevated by incretin-based therapies. Therefore, incretin-based therapies may exert direct extrapancreatic effects in order to protect blood vessels by enhancing anti-oxidative activity.
- Published
- 2016