AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis View Full Text


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Article Info

DATE

2016-01-25

AUTHORS

Xiling Zhang, Jian Yao, Kun Gao, Yuan Chi, Takahiko Mitsui, Tatsuya Ihara, Norifumi Sawada, Manabu Kamiyama, Jianglin Fan, Masayuki Takeda

ABSTRACT

Bladder voiding dysfunction is closely related to local oxidation, inflammation and enhanced channel activities. Given that the AMP-activated protein kinase (AMPK) has anti-oxidative, anti-inflammatory and channel-inhibiting properties, we examined whether and how AMPK affected bladder activity. AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation. Downregulation of CREB with siRNA increased Cx43 expression. A functional analysis revealed that AMPK weakened BSMC contraction and bladder capacity. AMPK also counteracted the IL-1β- and TNFα-induced increase in Cx43 in BSMCs. In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction. Further analysis comparing the responses of the wild-type (Cx43+/+) and heterozygous (Cx43+/−) Cx43 mice to cyclophosphamide revealed that the Cx43+/− mice retained a relatively normal micturition pattern compared to the Cx43+/+ mice. Taken together, our results indicate that AMPK inhibits Cx43 in BSMCs and improves bladder activity under pathological conditions. We propose that strategies that target AMPK can be developed as novel therapeutic approaches for treating bladder dysfunction. More... »

PAGES

19708

References to SciGraph publications

  • 2013-01-16. Metabolism of inflammation limited by AMPK and pseudo-starvation in NATURE
  • 2009-06-21. The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesis in NATURE
  • 2007-01-15. Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation in CELL BIOLOGY AND TOXICOLOGY
  • 2012-03-22. AMPK: a nutrient and energy sensor that maintains energy homeostasis in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2013-07-05. Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model in SCIENTIFIC REPORTS
  • 2005-09-07. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism in NATURE
  • 2002-08-16. Smooth muscle cells from human urinary bladder express connexin 43 in vivo and in vitro in WORLD JOURNAL OF UROLOGY
  • 2008-06. The neural control of micturition in NATURE REVIEWS NEUROSCIENCE
  • 2009-01-06. Changes of bladder activity and connexin 43-derived gap junctions after partial bladder-outlet obstruction in rats in INTERNATIONAL UROLOGY AND NEPHROLOGY
  • 2008-03-17. Involvement of hypoxia-triggered endoplasmic reticulum stress in outlet obstruction-induced apoptosis in the urinary bladder in LABORATORY INVESTIGATION
  • 2005-01-11. Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey (NHANES III) in INTERNATIONAL JOURNAL OF OBESITY
  • 2012-01. Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm in NATURE COMMUNICATIONS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/srep19708

    DOI

    http://dx.doi.org/10.1038/srep19708

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26806558


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    34 schema:description Bladder voiding dysfunction is closely related to local oxidation, inflammation and enhanced channel activities. Given that the AMP-activated protein kinase (AMPK) has anti-oxidative, anti-inflammatory and channel-inhibiting properties, we examined whether and how AMPK affected bladder activity. AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation. Downregulation of CREB with siRNA increased Cx43 expression. A functional analysis revealed that AMPK weakened BSMC contraction and bladder capacity. AMPK also counteracted the IL-1β- and TNFα-induced increase in Cx43 in BSMCs. In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction. Further analysis comparing the responses of the wild-type (Cx43+/+) and heterozygous (Cx43+/−) Cx43 mice to cyclophosphamide revealed that the Cx43+/− mice retained a relatively normal micturition pattern compared to the Cx43+/+ mice. Taken together, our results indicate that AMPK inhibits Cx43 in BSMCs and improves bladder activity under pathological conditions. We propose that strategies that target AMPK can be developed as novel therapeutic approaches for treating bladder dysfunction.
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