(013) Glycated Serum Albumin Decreases Connexin 43 Phosphorylation in the Corpus Cavernosum

Abstract

Abstract Introduction Glycated serum albumin (GSA) is an early glycosylation product that participates in diabetic vascular complications, including retinopathy, nephropathy, neuropathy, and coronary artery disease. Elevated GSA levels and the associated damage to the corpus cavernosum might be limited to not only diabetic patients but also non-diabetic patients and even individuals with normal glucose levels. Objective This study aimed to examine the role of GSA in early damage to the corpus cavernosum and identify the pathways involved in GSA-induced endothelium damage. Methods Nine 8-week-old male Sprague-Dawley (SD) rats (250–300 g) were divided into the control (saline vehicle, n=3) and GSA (200 μg/kg, n=6) groups. The corpus cavernosum tissues were harvested. Phosphorylated and non-phosphorylated connexin 43 (Cx43), endothelial nitric oxide synthase (eNOS), phosphatidylinositol 3-kinase (PI3K), and serine-threonine kinase (Akt) were tested by immunohistochemistry and western blotting. Human umbilical vein endothelial cells (HUVECs) overexpressing Cx43 were used to analyze the Cx43 phosphorylation sites (S368, S262, Y265, S255, and S279/282) using western blotting. Results The expression of phosphorylated Cx43 in the penis was significantly lower in GSA-treated rats than in controls. The expression levels of p-Cx43, p-eNOS, p-PI3K, and p-Akt were significantly decreased in HUVECs exposed to GSA in dose- and time-dependent manners. The most significant impact on all four proteins was observed with 1 μg/mL of GSA for 12 h. Phosphorylation at the S368, S262, Y265, S255, and S279/282 sites of Cx43 was downregulated by GSA, and S368 was the most significantly suppressed phosphorylation site compared with the other sites. Conclusions GSA decreases the expression of p-Cx43 in the corpus cavernosum of rats. This effect might be also related to the decreased phosphorylation of p-eNOS, p-PI3K, and p-Akt, as well as by the downregulation of phosphorylation at the S368 site. Disclosure No.