Sulforaphane Improves Ischemia-Induced Detrusor Overactivity by Downregulating the Enhancement of Associated Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Rat Bladder.
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.
Department of Urology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Graduate Institution of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Huai-Ching
HC
Tai
Graduate Institution of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Urology, Far East Memory Hospital, New Taipei City, Taiwan.|Graduate Program in Biomedical Informatics, College of Informatics, Yuan-Ze University, Chung-Li, Tao-Yuan, Taiwan.
Shiu-Dong
SD
Chung
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
Chiang-Ting
CT
Chien
Department of Urology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Hong-Jeng
HJ
Yu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007511:Ischemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017879:Isothiocyanates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013454:Sulfoxides; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology
D017879:Isothiocyanates; D013454:Sulfoxides; C016766:sulforaphane