ArticlePloS one2012
Aquaporin-1 translocation and degradation mediates the water transportation mechanism of acetazolamide.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- Role of vitamin A metabolism in IIH: Results from the idiopathic intracranial hypertension treatment trial.Journal of the neurological sciences · 2017Trial
- Are Procoagulant Platelets an Emerging Therapeutic Target? A General Review with an Emphasis on Their Clinical Significance in Companion Animals.International journal of molecular sciences · 2025Review
- The Role of Choroid Plexus in Hydrocephalus from the Perspective of Structure and Function: a Therapeutic Target.Molecular neurobiology · 2025Review
- Acetazolamide and human carbonic anhydrases: retrospect, review and discussion of an intimate relationship.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- Effects of furosemide, acetazolamide and amiloride on renal cortical and medullary tissue oxygenation in non-anaesthetised healthy sheep.Experimental physiology · 2024Article
- Autophagy is involved in degradation of AQP1 in response to an acute decrement in tonicity.iScience · 2023Article
- Aquaporin-mediated dysregulation of cell migration in disease states.Cellular and molecular life sciences : CMLS · 2023Review
- Alleviation of liver cirrhosis and associated portal-hypertension by Astragalus species in relation to their UPLC-MS/MS metabolic profiles: a mechanistic study.Scientific reports · 2022Article
- Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus.Fluids and barriers of the CNS · 2022Article
- Procoagulant platelets: Generation, characteristics, and therapeutic target.Journal of clinical laboratory analysis · 2021Review
- Myosin II and Arp2/3 cross-talk governs intracellular hydraulic pressure and lamellipodia formation.Molecular biology of the cell · 2021Article
- Modulation of Tubular pH by Acetazolamide in a CaInternational journal of molecular sciences · 2021Article
- Aquaporin 1 mediates early responses to osmotic stimuli in endothelial cells via the calmodulin pathway.FEBS open bio · 2021Article
- Combined Effect of Cold Atmospheric Plasma and Curcumin in Melanoma Cancer.BioMed research international · 2021Article
- The effects of the Xijiao Dihuang decoction combined with Yinqiao powder on miRNA-mRNA profiles in mice infected with influenza a virus.BMC complementary medicine and therapies · 2020Article
- AQP1 modulates tendon stem/progenitor cells senescence during tendon aging.Cell death & disease · 2020Article
- Potentially repurposable drugs for schizophrenia identified from its interactome.Scientific reports · 2019Article
- Inhibition of cell proliferation, migration and colony formation of LS174T Cells by carbonic anhydrase inhibitor.African health sciences · 2018Article
- Urinary Exosomes and Their Cargo: Potential Biomarkers for Mineralocorticoid Arterial Hypertension?Frontiers in endocrinology · 2017Review
- 3, 4-dihydroxyl-phenyl lactic acid restores NADH dehydrogenase 1 α subunit 10 to ameliorate cardiac reperfusion injury.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiuretic agents are widely used on the treatment of water retention related diseases, among which acetazolamide (AZA) acts originally as a carbonic anhydrase (CA) inhibitor. Aquaporin-1 (AQP1) being located in renal proximal tubules is required for urine concentration. Previously our lab has reported AZA putatively modulated AQP1. Aim of this study is to testify our hypothesis that regulating AQP1 may mediate diuretic effect of AZA. METHODOLOGY/PRINCIPAL
findingsFor in vivo study, we utilized Sprague Dawley rats, as well as AQP1 knock-out (AQP1(-/-)) mice to examine urine volume, and human kidney-2 (HK-2) cell line was used for in vitro mechanism study. In our present study we found that AZA decreased CAs activity initially but the activity gradually recovered. Contrarily, diuretic effect was consistently significant. AQP1 protein expression was significantly decreased on day 7 and 14. By utilizing AQP1(-/-) mice, we found diuretic effect of AZA was cancelled on day 14, while urine volume continuously increased in wild-type mice. Surface plasmon resonance (SPR) results indicated AQP1 was physiologically bound by myosin heavy chain (MHC), immunoprecipitation and immunofluorescence results confirmed this protein interaction. In vitro study results proved AZA facilitated AQP1 translocation onto cell membrane by promoting interaction with MHC, dependent on ERK/ myosin light chain kinase (MLCK) pathway activation. MHC inhibitor BDM and ERK inhibitor U0126 both abolished above effect of AZA. Eventually AZA induced AQP1 ubiquitination, while proteasome inhibitor MG132 reversed AZA's down-regulating effect upon AQP1. CONCLUSIONS/SIGNIFICANCE: Our results identified AZA exerted diuretic effect through an innovative mechanism by regulating AQP1 and verified its inhibitory mechanism was via promoting MHC-dependent translocation onto cell membrane and then ubiquitin mediated degradation, implicating a novel mechanism and target for diuretic agent discovering.
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