Molecular targets for diabetes mellitus-associated erectile dysfunction

Elizabeth Yohannes, Jinsook Chang, Moses T. Tar, Kelvin Davies, Mark R. Chance

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Protein expression profiles in rat corporal smooth muscle tissue were compared between animal models of streptozotocin-induced diabetes mellitus (STZ-DM) and agematched controls (AMCs) 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 two-dimensional 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 MetaCore™ suggested altered activity of transcriptional factors that are of too low abundance to be detected by the two-dimensional gel method. The proteins that were down-regulated with diabetes include isoforms of collagen that are precursors to fibril-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-γ, Serpinf1, Cct4, Cct5, and Sepina3n), proteins that neutralize the biological activity of nerve growth factor (e.g. anti-NGF 30), and proteins involved in lipid metabolism (e.g. apoA-I and apoA-IV). Subsequent Western blot validation analysis of p53, 14-3-3-γ, and Hsp47 confirmed increased p53 and 14-3-3-γ 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.

Original languageEnglish (US)
Pages (from-to)565-578
Number of pages14
JournalMolecular and Cellular Proteomics
Volume9
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Erectile Dysfunction
Medical problems
Diabetes Mellitus
Proteins
Experimental Diabetes Mellitus
Nerve Growth Factor
Streptozocin
Western Blotting
Gels
Rat control
Tissue
Apolipoproteins A
Procollagen
Apolipoprotein A-I
Gonadal Steroid Hormones
Electric network analysis
Collagen Type I
Bioactivity
Lipid Metabolism
Hyperglycemia

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Cite this

Molecular targets for diabetes mellitus-associated erectile dysfunction. / Yohannes, Elizabeth; Chang, Jinsook; Tar, Moses T.; Davies, Kelvin; Chance, Mark R.

In: Molecular and Cellular Proteomics, Vol. 9, No. 3, 03.2010, p. 565-578.

Research output: Contribution to journalArticle

Yohannes, Elizabeth ; Chang, Jinsook ; Tar, Moses T. ; Davies, Kelvin ; Chance, Mark R. / Molecular targets for diabetes mellitus-associated erectile dysfunction. In: Molecular and Cellular Proteomics. 2010 ; Vol. 9, No. 3. pp. 565-578.
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