Aquaporin-3 (AQP3) is a membrane channel with dual aquaglyceroporin/peroxiporin activity, facilitating the diffusion of water, glycerol and HO across cell membranes. AQP3 shows aberrant expression in melanoma and its role in cell adhesion, migration and proliferation is well described. Gold compounds were shown to modulate AQP3 activity with reduced associated toxicity, making them promising molecules for cancer therapy.
View Article and Find Full Text PDFThe natural polyphenolic compound Rottlerin (RoT) showed anticancer properties in a variety of human cancers through the inhibition of several target molecules implicated in tumorigenesis, revealing its potential as an anticancer agent. Aquaporins (AQPs) are found overexpressed in different types of cancers and have recently emerged as promising pharmacological targets. Increasing evidence suggests that the water/glycerol channel aquaporin-3 (AQP3) plays a key role in cancer and metastasis.
View Article and Find Full Text PDFAquaglyceroporins, a sub-class of aquaporins that facilitate the diffusion of water, glycerol and other small uncharged solutes across cell membranes, have been recognized for their important role in human physiology and their involvement in multiple disorders, mostly related to disturbed energy homeostasis. Aquaglyceroporins dysfunction in a variety of pathological conditions highlighted their targeting as novel therapeutic strategies, boosting the search for potent and selective modulators with pharmacological properties. The identification of selective inhibitors with potential clinical applications has been challenging, relying on accurate assays to measure membrane glycerol permeability and validate effective functional blockers.
View Article and Find Full Text PDFThe inhibition of glycerol permeation via human aquaporin-10 (hAQP10) by organometallic gold complexes has been studied by stopped-flow fluorescence spectroscopy, and its mechanism has been described using molecular modelling and atomistic simulations. The most effective hAQP10 inhibitors are cyclometalated Au(III) C^N compounds known to efficiently react with cysteine residues leading to the formation of irreversible C-S bonds. Functional assays also demonstrate the irreversibility of the binding to hAQP10 by the organometallic complexes.
View Article and Find Full Text PDFSkin is the most vulnerable organ of the human body since it is the first line of defense, covering the entire external body surface. Additionally, skin has a critical role in thermoregulation, sensation, immunological surveillance, and biochemical processes such as Vitamin D production by ultraviolet irradiation. The ability of the skin layers and resident cells to maintain skin physiology, such as hydration, regulation of keratinocytes proliferation and differentiation and wound healing, is supported by key proteins such as aquaporins (AQPs) that facilitate the movements of water and small neutral solutes across membranes.
View Article and Find Full Text PDFThe regulation of glycerol permeability in the gastrointestinal tract is crucial to control fat deposition, lipolysis and gluconeogenesis. Knowing that the amino acid glutamine is a physiological regulator of gluconeogenesis, whereas cystine promotes adiposity, herein we investigated the effects of dietary supplementation with glutamine and cystine on the serum biochemical parameters of piglets fed on amino acid-enriched diets, as well as on the transcriptional profile of membrane water and glycerol channels aquaporins (AQPs) in the ileum portion of the small intestine and its impact on intestinal permeability. Twenty male piglets with an initial body weight of 8.
View Article and Find Full Text PDFPolyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells-Dawson PW, PW, and PW, and Preyssler PW structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration.
View Article and Find Full Text PDFReactive oxygen species (ROS), including HO, contribute to oxidative stress and may cause cancer initiation and progression. However, at low concentrations, HO can regulate signaling pathways modulating cell growth, differentiation, and migration. A few mammalian aquaporins (AQPs) facilitate HO diffusion across membranes and participate in tumorigenesis.
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