Smooth muscle-specific deletion of MnSOD exacerbates diabetes-induced bladder dysfunction in mice.
Am J Physiol Renal Physiol
; 317(4): F906-F912, 2019 10 01.
Article
em En
| MEDLINE
| ID: mdl-31241994
ABSTRACT
Bladder dysfunction in diabetes progresses gradually over time. However, the mechanisms of the development are not clear. We tested the hypothesis that oxidative stress plays a key role in the development of diabetic bladder dysfunction using an inducible smooth muscle (SM)-specific superoxide dismutase 2 (Sod2) gene knockout (SM-Sod2 KO) mouse model. Eight-week-old male Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice and wild-type mice were assigned to diabetic or control groups. 4-Hydroxytamoxifen was injected into Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice to activate CreERT2-mediated deletion of Sod2. Diabetes was induced by injection of streptozotocin, whereas control mice were injected with vehicle. Nine weeks later, bladder function was evaluated, and bladders were harvested for immunoblot analysis. Wild-type diabetic mice presented compensated bladder function along with increased nitrotyrosine and MnSOD in detrusor muscle. Induction of diabetes in SM-Sod2 KO mice caused deteriorated bladder function and even greater increases in nitrotyrosine compared with wild-type diabetic mice. Expression levels of apoptosis regulator Bax and cleaved caspase-3 were increased, but apoptosis regulator Bcl-2 expression was decreased in detrusor muscle of both diabetic groups, with more pronounced effects in SM-Sod2 KO diabetic mice. Our findings demonstrate that exaggerated oxidative stress can accelerate the development of bladder dysfunction in diabetic mice and the enhanced activation of apoptotic pathways in the bladder may be involved in the process.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Superóxido Dismutase
/
Doenças da Bexiga Urinária
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Diabetes Mellitus Experimental
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Músculo Liso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article