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Molecular targets for diabetes mellitus-associated erectile dysfunction.

ABSTRACT: 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 (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-gamma, 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-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 approximately 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.

SUBMITTER: Yohannes E

PROVIDER: S-EPMC2849705 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Molecular targets for diabetes mellitus-associated erectile dysfunction.

Yohannes Elizabeth E Chang Jinsook J Tar Moses T MT Davies Kelvin P KP Chance Mark R MR

Molecular & cellular proteomics : MCP 20091210 3

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 (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 ...[more]

PMID: 20007950

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Project description:Protein expression profiles in rat bladder smooth muscle were compared between animal models of streptozotocin-induced diabetes mellitus (STZ-DM) and age-matched controls 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 age-matched control rat bladder tissues were prepared independently and analyzed together across multiple DIGE gels using a pooled internal standard sample to quantify expression changes with statistical confidence. A total of 100 spots were determined to be significantly changing among the four experimental groups. A subsequent mass spectrometry analysis of the 100 spots identified a total of 56 unique proteins. Of the proteins identified by two-dimensional DIGE/MS, 10 exhibited significant changes 1 week after STZ-induced hyperglycemia, whereas the rest showed differential expression after 2 months. A network analysis of these proteins using MetaCore suggested induction of transcriptional factors that are too low to be detected by two-dimensional DIGE and identified an enriched cluster of down-regulated proteins that are involved in cell adhesion, cell shape control, and motility, including vinculin, intermediate filaments, Ppp2r1a, and extracellular matrix proteins. The proteins that were up-regulated include proteins involved in muscle contraction (e.g. Mrlcb and Ly-GDI), in glycolysis (e.g. alpha-enolase and Taldo1), in mRNA processing (e.g. heterogeneous nuclear ribonucleoprotein A2/B1), in inflammatory response (e.g. S100A9, Annexin 1, and apoA-I), and in chromosome segregation and migration (e.g. Tuba1 and Vil2). Our results suggest that the development of diabetes-related complications in this model involves the down-regulation of structural and extracellular matrix proteins in smooth muscle that are essential for normal muscle contraction and relaxation but also induces proteins that are associated with cell proliferation and inflammation that may account for some of the functional deficits known to occur in diabetic complications of bladder.

Project description:IntroductionExperiences and determinants connected with type 2 diabetes mellitus-associated erectile dysfunction (T2DMED) in health appointments are not well understood and infrequently reported. This systematic review was undertaken to synthesise evidence of the experiences, facilitators, and barriers around screening ED in men with T2DM during health service consultations.MethodsThe review report was based on the guidelines provided by the Joanna Briggs Institute for conducting mixed-method systematic reviews. Eight electronic databases were searched, including Web of Science, Embase via Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO, ProQuest, PubMed, PsychInfo via Ovid, MEDLINE via Ovid, Portal Garuda. Additionally, the review manually looked through the reference lists of the studies we included. Erectile dysfunction, type 2 diabetes mellitus, screening and barriers were initially used as keywords in the search strategy. All identified primary studies written in English and Bahasa Indonesia, and published between 2001 and 2022 were meticulously screened following an agreed set of inclusion criteria.FindingsOut of 3468 papers screened, only six were chosen for the review. These included three cross-sectional studies, two qualitative studies, and one mixed-method study. The study quality of the included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. Based on the checklist criteria, the studies ranged between 5/10 to 9/10 in terms of quality. After synthesizing the findings, four main categories were identified including the willingness to discuss T2DMED, the barriers experienced and perceived, the limited understanding of T2DMED, and the support expected by men with T2DM.DiscussionMany men kept quiet about their struggles with T2DMED, hoping to bring it up as a topic of discussion during healthcare consultations. Barriers such as embarrassment, a sense of helplessness and reluctance to seek help, financial constraints, and dismissive healthcare professionals hindered them from addressing this issue. Both the participating men and healthcare professionals lacked a comprehensive understanding of T2DMED.RecommendationsIt is important to provide education tailored to men's specific needs and improve awareness about T2DM-associated ED. Creating a more T2DMED-friendly environment could be a potential solution to increase early screening and management. Future research should investigate potential barriers that prevent HCPs from identifying and addressing T2MED since their absence in the identified studies highlights this need.Systematic review registrationCRD42021292454.

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Molecular targets for diabetes mellitus-associated erectile dysfunction.

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Molecular targets for diabetes mellitus-associated erectile dysfunction.

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