D-4F induces heme oxygenase-1 and extracellular superoxide dismutase, decreases endothelial cell sloughing, and improves vascular reactivity in rat model of diabetes

Autor: Michael S. Wolin, Saadet Turkseven, Nader G. Abraham, Pawel M. Kaminski, Shuo Quan, Stephen J. Peterson, Frank Zhang, Adam Kruger
Rok vydání: 2005
Předmět:
Zdroj: Circulation. 111(23)
ISSN: 1524-4539
Popis: Background— Apolipoprotein A1 mimetic peptide, synthesized from D-amino acid (D-4F), enhances the ability of HDL to protect LDL against oxidation in atherosclerotic animals. Methods and Results— We investigated the mechanisms by which D-4F provides antioxidant effects in a diabetic model. Sprague-Dawley rats developed diabetes with administration of streptozotocin (STZ). We examined the effects of daily D-4F (100 μg/100 g of body weight, intraperitoneal injection) on superoxide (O 2 − ), extracellular superoxide dismutase (EC-SOD), vascular heme oxygenase (HO-1 and HO-2) levels, and circulating endothelial cells in diabetic rats. In response to D-4F, both the quantity and activity of HO-1 were increased. O 2 − levels were elevated in diabetic rats (74.8±8×10 3 cpm/10 mg protein) compared with controls (38.1±8×10 3 cpm/10 mg protein; P 2 − levels to 13.23±1×10 3 ( P P Conclusions— We conclude that an increase in circulating endothelial cell sloughing, superoxide anion, and vasoconstriction in diabetic rats can be prevented by administration of D-4F, which is associated with an increase in 2 antioxidant proteins, HO-1 and EC-SOD.
Databáze: OpenAIRE