Suppression of 15-Hydroxyprostaglandin Dehydrogenase Messenger RNA Concentration, Protein Expression, and Enzymatic Activity during Human Ureteral Obstruction

Travis Jerde, William S. Mellon, Susan M. Fischer, Monica Liebert, Dale E. Bjorling, Stephen Y. Nakada

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Prostanoids produce significant effects in the ureter, particularly in response to obstruction. Ureteral obstruction is associated with increased prostanoid synthesis via cyclooxygenase induction; however, prostaglandin degradation mediated by 15-hydroxyprostaglandin dehydrogenase (PGDH) has not been evaluated in the ureter. The purpose of this study was to determine whether PGDH steady-state mRNA, protein, and enzyme activity are altered in the human ureter during obstruction. Human ureteral segments from patients undergoing donor nephrectomy (normal segments) or ureteral stricture repair (obstructed segments) were obtained with proper informed consent. We evaluated PGDH steady-state mRNA relative to ribosomal protein S26 reference gene by reverse transcription-polymerase chain reaction and Vistra Green fluoroimaging. We determined PGDH protein content relative to glyceraldehyde-3-phosphate dehydrogenase by immunoblotting and PGDH localization by immunohistochemistry. PGDH enzymatic activity was determined by measurement of conversion of 15-hydroxy- to 15-keto-prostaglandin using thin layer chromatography separation. We found that PGDH mRNA and protein were decreased 4- to 6-fold, and enzyme activity was decreased >3-fold in obstructed human ureter relative to normal controls. PGDH was localized to the urothelial cells, with little or no expression in smooth muscle. Our results indicate that PGDH mRNA, protein, and enzyme activity are suppressed in the human ureter during obstruction. Increased concentrations of prostanoids subsequent to ureteral obstruction seem to be due to decreased degradation as well as increased synthesis. Modulation of prostanoid degradation may have therapeutic relevance in obstructive disorders of the ureter.

Original languageEnglish (US)
Pages (from-to)398-403
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume309
Issue number1
DOIs
StatePublished - Apr 2004
Externally publishedYes

Fingerprint

15-hydroxyprostaglandin dehydrogenase
Ureteral Obstruction
Ureter
Human Activities
Prostaglandins
Messenger RNA
Proteins
Enzymes
Glyceraldehyde-3-Phosphate Dehydrogenases
Ribosomal Proteins
Prostaglandin-Endoperoxide Synthases
Thin Layer Chromatography
Nephrectomy
Informed Consent
Immunoblotting
Reverse Transcription
Smooth Muscle
Pathologic Constriction
Immunohistochemistry
Tissue Donors

ASJC Scopus subject areas

  • Pharmacology

Cite this

Suppression of 15-Hydroxyprostaglandin Dehydrogenase Messenger RNA Concentration, Protein Expression, and Enzymatic Activity during Human Ureteral Obstruction. / Jerde, Travis; Mellon, William S.; Fischer, Susan M.; Liebert, Monica; Bjorling, Dale E.; Nakada, Stephen Y.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 309, No. 1, 04.2004, p. 398-403.

Research output: Contribution to journalArticle

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