MP76-07 IMPAIRMENT IN P2X2 PURINERGIC SIGNALING AND UP-REGULATING AAPOPTOSIS, AUTOPHAGY AND PYROPTOSIS CONTRIBUTE TO BLADDER DYSFUNCTION AFTER LONG-TERM HIGH-FAT DIET

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Non-neurogenic Voiding Dysfunction1 Apr 2014MP76-07 IMPAIRMENT IN P2X2 PURINERGIC SIGNALING AND UP-REGULATING AAPOPTOSIS, AUTOPHAGY AND PYROPTOSIS CONTRIBUTE TO BLADDER DYSFUNCTION AFTER LONG-TERM HIGH-FAT DIET Po Wen Ku and Shiu Dong Chung Po Wen KuPo Wen Ku More articles by this author and Shiu Dong ChungShiu Dong Chung More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2400AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Three types of programmed cell death, apoptosis, autophagy and pyroptosis may contribute to high-fat diet induced lower urinary tract symptom including bladder dysfunction. METHODS Hyperlipidemia was induced in healthy Male Wistar rats by a high fat diet (HFD) for 3 or 6 months. Bladder function was assessed by 24-hour voiding behavior study with a conscious cystometry and by a transcystogram under anesthesia. Biochemical parameters and the molecular mechanisms involving programmed cell death and bladder contractile pathway by western blot were evaluated between HFD and aged-matched normal-diet rats. Bladder histology was assessed using immunostaining. RESULTS Serum total cholesterol, low density lipoprotein and triglyceride were significantly higher in HFD rats than in normal rats (P<0.01). A shorter intercontraction interval and an elongated phase 2 contractile interval were found in HFD rats than in normal rats (P<0.05). The contractile amplitude (value= maximal voiding pressure baseline intravesical pressure) was significantly (P<0.05) depressed after HFD. HFD induced morphologic alteration in the smooth muscle and blood vessels and increased fibrosis appearance in the impaired bladder. By western blotting analysis, Bax/caspase 3/poly ADP-ribose polymerase (PARP) mediated apoptosis, Beclin-1 mediated autophagy, and caspase-1 mediated pyroptosis were all significantly (P<0.05) elevated in HFD rats vs normal diet rats. However, muscarinic receptor M2 and M3 expressions were not affected after HFD. HFD significantly reduced bladder ATP not acetylcholine content and enhanced protein expression of postsynaptic P2X2, not P2X3 purinergic receptors and M2 and M3 muscarinic cholinergic receptors in the smooth muscles of urinary bladder. The highly expressed P2X2, Bax, Beclin-1 and caspase 1 were all confirmed by the immunohistochemistry. CONCLUSIONS Long-term HFD induced bladder dysfunction was ascribed to the impairment in P2X2 mediated purinergic signaling and associated with the increased appearance of three types of programmed cell death in the urinary bladder. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e884 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Po Wen Ku More articles by this author Shiu Dong Chung More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...