Sulforaphane Improves Ischemia-Induced Detrusor Overactivity by Downregulating the Enhancement of Associated Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Rat Bladder

Huai Ching Tai, Shiu Dong Chung, Chiang Ting Chien, Hong Jeng Yu

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3 Citations (Scopus)

Abstract

Atherosclerosis-associated pelvic ischemia has been reported to be a risk factor for bladder dysfunction and subsequent lower urinary tract symptoms (LUTS) in the elderly population. However, the molecular mechanisms of this association remain unclear. We hypothesized that stress-induced cellular responses might play a role in the pathogenesis of ischemia-induced bladder dysfunction. In the present study, the animal model of bladder ischemia was induced by bilateral partial arterial occlusion (BPAO) in rats. We found that BPAO significantly induced the presence of detrusor overactivity (DO) and upregulated the expression of several molecular reactions, including biomarkers in endoplasmic reticulum stress (78 kDa glucose-regulated protein, GRP78 and C/EBP-homologous protein, CHOP), autophagy (Beclin-1, p62 and LC3 II) and apoptosis (caspase 3). BPAO also disturbed the Kelch-like ECH-associated protein 1-nuclear factor erythroid-2-related factor 2 (Keap1-Nrf2) pathways. These responses might collectively alter muscarinic and purinergic signaling and contribute to the presence of DO in the ischemic bladder. Therapeutically, treatment with neither a muscarinic nor purinergic receptor antagonist restored bladder function. Interestingly, sulforaphane effectively attenuated ischemia-enhanced endoplasmic reticulum stress, autophagy and apoptosis in the bladder, subsequently ameliorated ischemia-induced bladder dysfunction and might emerge as a novel strategy to protect the bladder against ischemia-induced oxidative damage.

Original languageEnglish
Article number36110
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016 Nov 8

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Endoplasmic Reticulum Stress
Autophagy
Urinary Bladder
Down-Regulation
Ischemia
Apoptosis
Cholinergic Agents
Purinergic Antagonists
Transcription Factor CHOP
Lower Urinary Tract Symptoms
sulforafan
Protein C
Caspase 3
Atherosclerosis
Animal Models
Biomarkers
Glucose

ASJC Scopus subject areas

  • General

Cite this

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title = "Sulforaphane Improves Ischemia-Induced Detrusor Overactivity by Downregulating the Enhancement of Associated Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Rat Bladder",
abstract = "Atherosclerosis-associated pelvic ischemia has been reported to be a risk factor for bladder dysfunction and subsequent lower urinary tract symptoms (LUTS) in the elderly population. However, the molecular mechanisms of this association remain unclear. We hypothesized that stress-induced cellular responses might play a role in the pathogenesis of ischemia-induced bladder dysfunction. In the present study, the animal model of bladder ischemia was induced by bilateral partial arterial occlusion (BPAO) in rats. We found that BPAO significantly induced the presence of detrusor overactivity (DO) and upregulated the expression of several molecular reactions, including biomarkers in endoplasmic reticulum stress (78 kDa glucose-regulated protein, GRP78 and C/EBP-homologous protein, CHOP), autophagy (Beclin-1, p62 and LC3 II) and apoptosis (caspase 3). BPAO also disturbed the Kelch-like ECH-associated protein 1-nuclear factor erythroid-2-related factor 2 (Keap1-Nrf2) pathways. These responses might collectively alter muscarinic and purinergic signaling and contribute to the presence of DO in the ischemic bladder. Therapeutically, treatment with neither a muscarinic nor purinergic receptor antagonist restored bladder function. Interestingly, sulforaphane effectively attenuated ischemia-enhanced endoplasmic reticulum stress, autophagy and apoptosis in the bladder, subsequently ameliorated ischemia-induced bladder dysfunction and might emerge as a novel strategy to protect the bladder against ischemia-induced oxidative damage.",
author = "Tai, {Huai Ching} and Chung, {Shiu Dong} and Chien, {Chiang Ting} and Yu, {Hong Jeng}",
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AU - Tai, Huai Ching

AU - Chung, Shiu Dong

AU - Chien, Chiang Ting

AU - Yu, Hong Jeng

PY - 2016/11/8

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AB - Atherosclerosis-associated pelvic ischemia has been reported to be a risk factor for bladder dysfunction and subsequent lower urinary tract symptoms (LUTS) in the elderly population. However, the molecular mechanisms of this association remain unclear. We hypothesized that stress-induced cellular responses might play a role in the pathogenesis of ischemia-induced bladder dysfunction. In the present study, the animal model of bladder ischemia was induced by bilateral partial arterial occlusion (BPAO) in rats. We found that BPAO significantly induced the presence of detrusor overactivity (DO) and upregulated the expression of several molecular reactions, including biomarkers in endoplasmic reticulum stress (78 kDa glucose-regulated protein, GRP78 and C/EBP-homologous protein, CHOP), autophagy (Beclin-1, p62 and LC3 II) and apoptosis (caspase 3). BPAO also disturbed the Kelch-like ECH-associated protein 1-nuclear factor erythroid-2-related factor 2 (Keap1-Nrf2) pathways. These responses might collectively alter muscarinic and purinergic signaling and contribute to the presence of DO in the ischemic bladder. Therapeutically, treatment with neither a muscarinic nor purinergic receptor antagonist restored bladder function. Interestingly, sulforaphane effectively attenuated ischemia-enhanced endoplasmic reticulum stress, autophagy and apoptosis in the bladder, subsequently ameliorated ischemia-induced bladder dysfunction and might emerge as a novel strategy to protect the bladder against ischemia-induced oxidative damage.

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