Impairment of AMPK-α2 augments detrusor contractions in bladder ischemia
| Autor: | Jing-Hua Yang, Kazem M. Azadzoi, Wanting Niu, Yedan Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Urology Urinary Bladder Ischemia ischemia AMP-Activated Protein Kinases Contractility peripheral arterial disease Internal medicine overactive detrusor medicine Animals Protein kinase A bladder Basic/Translational Research business.industry Balloon catheter AMPK medicine.disease Adenosine Diseases of the genitourinary system. Urology Rats Endocrinology Original Article metabolic stress RC870-923 business Homeostasis Immunostaining Muscle Contraction medicine.drug |
| Zdroj: | Investigative and Clinical Urology, Vol 62, Iss 5, Pp 600-609 (2021) Investigative and Clinical Urology |
| ISSN: | 2466-0493 |
| DOI: | 10.4111/icu.20210095 |
| Popis: | Purpose Ischemia disrupts cellular energy homeostasis. Adenosine monophosphate-activated protein kinase alpha-2 (AMPK-α2) is a subunit of AMPK that senses cellular energy deprivation and signals metabolic stress. Our goal was to examine the expression levels and functional role of AMPK-α2 in bladder ischemia. Materials and Methods Iliac artery atherosclerosis and bladder ischemia were engendered in apolipoprotein E knockout rats by partial arterial endothelial denudation using a balloon catheter. After eight weeks, total and phosphorylated AMPK-α2 expression was analyzed by western blotting. Structural integrity of AMPK-α2 protein was assessed by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Functional role of AMPK-α2 was examined by treating animals with the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D ribofuranoside (AICAR). Tissue contractility was measured in the organ bath and bladder nerve density was examined by immunostaining. Results Total AMPK-α2 expression increased in bladder ischemia, while phosphorylated AMPK-α2 was significantly downregulated. LC-MS/MS suggested post-translational modification of AMPK-α2 functional domains including phosphorylation sites, suggesting accumulation of catalytically inactive AMPK-α2 in bladder ischemia. Treatment of rats with AICAR diminished the force of overactive detrusor contractions and increased bladder capacity but did not have a significant effect on the frequency of bladder contractions. AICAR diminished contractile reactivity of ischemic tissues in the organ bath and prevented loss of nerve fibers in bladder ischemia. Conclusions Ischemia induces post-translational modification of AMPK-α2 protein. Impairment of AMPK-α2 may contribute to overactive detrusor contractions and loss of nerve fibers in bladder ischemia. AMPK activators may have therapeutic potential against detrusor overactivity and neurodegeneration in bladder conditions involving ischemia. Graphical Abstract |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|