Proteomics analysis identifies molecular targets related to diabetes mellitus-associated bladder dysfunction

Elizabeth Yohannes, Jinsook Chang, George J. Christ, Kelvin Davies, Mark R. Chance

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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 hyper-glycemia 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. MrIcb and Ly-GDI), in glycolysis (e.g. α-enolase and Taldo1), in mRNA processing (e.g. heterogeneous nuclear ribonucleoprotein A2/B1), in inflammatory response (e.g. S100A9, Annexin 1, and apoA-1), 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.

Original languageEnglish (US)
Pages (from-to)1270-1285
Number of pages16
JournalMolecular and Cellular Proteomics
Volume7
Issue number7
DOIs
StatePublished - Jul 2008

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Medical problems
Proteomics
Diabetes Mellitus
Urinary Bladder
Proteins
Muscle
Experimental Diabetes Mellitus
Extracellular Matrix Proteins
Diabetes Complications
Streptozocin
Muscle Contraction
Smooth Muscle
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
Guanine Nucleotide Dissociation Inhibitors
Rat control
Vinculin
Annexins
Chromosome Segregation
Muscle Relaxation
Intermediate Filaments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Proteomics analysis identifies molecular targets related to diabetes mellitus-associated bladder dysfunction. / Yohannes, Elizabeth; Chang, Jinsook; Christ, George J.; Davies, Kelvin; Chance, Mark R.

In: Molecular and Cellular Proteomics, Vol. 7, No. 7, 07.2008, p. 1270-1285.

Research output: Contribution to journalArticle

Yohannes, Elizabeth ; Chang, Jinsook ; Christ, George J. ; Davies, Kelvin ; Chance, Mark R. / Proteomics analysis identifies molecular targets related to diabetes mellitus-associated bladder dysfunction. In: Molecular and Cellular Proteomics. 2008 ; Vol. 7, No. 7. pp. 1270-1285.
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