Back to Search Start Over

Enhanced RAGE Expression and Excess Reactive-Oxygen Species Production Mediates Rho Kinase-Dependent Detrusor Overactivity After Methylglyoxal Exposure.

Authors :
Oliveira AL
Medeiros ML
de Oliveira MG
Teixeira CJ
Mónica FZ
Antunes E
Source :
Frontiers in physiology [Front Physiol] 2022 Mar 28; Vol. 13, pp. 860342. Date of Electronic Publication: 2022 Mar 28 (Print Publication: 2022).
Publication Year :
2022

Abstract

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound implicated in diabetes-associated diseases. In vascular tissues, MGO induces the formation of advanced glycation end products (AGEs) that bounds its receptor RAGE, initiating the downstream tissue injury. Outside the cardiovascular system, MGO intake produces mouse voiding dysfunction and bladder overactivity. We have sought that MGO-induced bladder overactivity is due to activation of AGE-RAGE-reactive-oxygen species (ROS) signaling cascade, leading to Rho kinase activation. Therefore, female mice received 0.5% MGO orally for 12 weeks, after which in vitro bladder contractions were evaluated in the presence or not of superoxide dismutase (PEG-SOD) or the Rho kinase inhibitor Y27632. Treatment with MGO significantly elevated the serum levels of MGO and fluorescent AGEs, as well as the RAGE immunostaining in the urothelium, detrusor, and vascular endothelium. RAGE mRNA expression in the bladder was also higher in the MGO group. Methylglyoxal significantly increased the ROS production in both urothelium and detrusor smooth muscle, with the increases in detrusor markedly higher than urothelium. The bladder activity of superoxide dismutase (SOD) was significantly reduced in the MGO group. Gene expressions of L-type Ca <superscript>2+</superscript> channels, RhoA, ROCK-1, and ROCK-2 in bladder tissues were significantly elevated in the MGO group. Increased bladder contractions to electrical-field stimulation, carbachol α,β-methylene ATP, and extracellular Ca <superscript>2+</superscript> were observed after MGO exposure, which was significantly reduced by prior incubation with either PEG-SOD or Y27632. Overall, our data indicate serum MGO accumulation elevates the AGEs levels and activates the RAGE-ROS signaling leading to Rho kinase-induced muscle sensitization, ultimately leading to detrusor overactivity.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2022 Oliveira, Medeiros, de Oliveira, Teixeira, Mónica and Antunes.)

Details

Language :
English
ISSN :
1664-042X
Volume :
13
Database :
MEDLINE
Journal :
Frontiers in physiology
Publication Type :
Academic Journal
Accession number :
35418871
Full Text :
https://doi.org/10.3389/fphys.2022.860342