Molecular targets for diabetes mellitus associated erectile dysfunction

Dec. 22, 2009

Protein expression profiles in rat corporal smooth muscle tissue were compared between animal models of streptozotocin-induced diabetes mellitus (STZ-DM) and age matched controls (AMC) at 1 week and 2 months after induction of hyperglycemia with STZ treatment. At each time point, protein samples from four STZ-DM and four AMC rat corpora tissues were prepared independently and analyzed together across multiple quantitative 2-D gels using a pooled internal standard sample to quantify expression changes with statistical confidence. A total of 170 spots were differential expressed among the four experimental groups. A subsequent mass spectrometry analysis of the 170 spots identified a total of 57 unique proteins. Network analysis of these proteins using MetacoreTM suggested altered activity of transcriptional factors that are of too low abundance to be detected by the 2D-gel method. The proteins that were down regulated with diabetes include: isoforms of collagen that are precursors to fibrils forming collagen type 1; Hsp47, which assists and mediates the proper folding of procollagen; and several proteins whose abundance is controlled by sex hormones (e.g., CRP1, and A2U). On the other hand, proteins seen or predicted to be up regulated include: proteins involved in cell apoptosis (e.g., p53, 14-3-3-gamma, Serpinf1, Cct4, Cct5, and Sepina3n); proteins that neutralize the biological activity of nerve growth factor (eg. Anti-NGF 30); and proteins involved in lipid metabolism (e.g., ApoA1 and ApoA4). Subsequent Western blot validation analysis of p53, 14-3-3 gamma, and Hsp47 confirmed increased p53 and 14-3-3 gamma and decreased Hsp47 levels in separate samples. According to the results from the western blot analysis, Hsp47 protein showed a ~3-fold decrease at 1 week and was virtually undetectable at 2 months in diabetic versus control. Taken together, our results identify novel candidate proteins playing a role in erectile dysfunction in diabetes resulting from STZ-treatment.

Elizabeth Yohannes, Jinsook Chang, Moses T. Tar, Kelvin P. Davies, and Mark R. Chance, "Molecular targets for diabetes mellitus associated erectile dysfunction," Mol. Cell. Proteomics, December 10, 2009; doi:10.1074/mcp.M900286-MCP200.