Aqps were first described by peter agre, an american physician and molecular biologist, while studying red blood cell membranes and the rhesus group. The expression of aqps has been found in more than 20 human cancer types and is significantly correlated with the severity of histological tumors and prognosis of patients with cancer. The aquaporins are a family of membrane water channels, some of which alsotransport glycerol. Genetic diseases caused by lossoffunction mutations in aquaporins include. Departments of medicine and physiology, cardiovascular research institute, room 1246, box 0521 university of california. Aquaporins are integral membrane proteins that facilitate the diffusion of water and other small, uncharged solutes across the cellular membrane and are widely distributed in organisms from humans to bacteria. Aquaporin water channels from atomic structure to clinical. The molecular identity of the first water channel, aquaporin 1 aqp1, was reported. Aquaporins ion channels iupharbps guide to pharmacology.
Aquaporins are protein channels that facilitate the flow of water across plasma cell membranes in response to osmotic gradients. The aquaporins are a family of membrane water channels, some of which also transport. The aquaporins are a family of membrane water channels, some of which also transport glycerol. Aquaporins, as indicated by their name, are water channel molecules that allow water to cross the hydrophobic lipid bilayers of cellular membranes. Aquaporins are a diverse family of membrane proteins that are expressed predominantly in tissues in which edema and fluid imbalances are of major concern.
The discovery of aqp4 autoantibodies as a marker of the neuromyelitis optica form of multiple sclerosis has allowed precise diagnosis of this disease. The expanding role of vesicles containing aquaporins mdpi. Aquaporins often called aquaporin water channels are a family of small, integral membrane proteins that are expressed broadly throughout the animal and plant kingdoms. Adding multimedia alexion receives fda approval of soliris. They are involved in a wide range of physiological functions including watersalt homeostasis, exocrine fluid secretion, and epidermal hydration and human diseases including glaucoma, cancer, epilepsy, and obesity.
Aquaporins in clinical medicine europe pmc article. What are the risk factors for diabetes insipidus di. However, the characteristics of prokaryotic aquaporins remain largely unknown. Verkman, departments of medicine and physiology, university of.
The aquaporins aqps are a family of water channels that are conserved throughout the animal and plant kingdoms, and in lower organisms. Defective proximal tubular fluid reabsorption in transgenic aquaporin1 null mice. However, important unanswered questions remainfor example, we do not know. They are involved in a wide range of physiological functions including watersalt homeostasis, exocrine i uid secretion, and epidermal hydration and. Aquaporins and cftr in ocular epithelial fluid transport.
Effect of abnormal savda munziq, a traditional uighur herbal. They are involved in a wide range of physiological functions including watersalt homeostasis, exocrine i uid secretion, and epidermal hydration and human diseases including glaucoma, cancer. The sites of expression coincide closely with the clinical phenotypes ranging from congenital cataracts to nephrogenic diabetes insipidus. We investigated the distribution and sequence characterization of aquaporins in prokaryotic organisms and. At the cellular level, aquaporinmediated osmotic water transport across cell. Aqp4 is the most abundant water channel in the brain 27, spinal cord 28 and optic nerve 29. Download citation aquaporins in clinical medicine the aquaporins are a. An emerging paradigm in molecular medicine is the therapy of protein folding.
Aquaporins are targets for drug discovery for basic research and medicine. Key roles of aquaporins in tumor biology sciencedirect. Aquaporins aqps are a family of water channel proteins distributed in. They are involved in a wide range of physiological functions including watersalt homeostasis, exocrine fluid secretion, and epidermal hydration and human diseases. Verkman aquaporins have multiple distinct roles in mammalian physiology. Roles for novel pharmacological blockers of aquaporins in the. Aquaporins as potential drug targets acta pharmacologica sinica. Aquaporins are multifunctional water and solute transporters highly divergent in living organisms. Verkman departments of medicine and physiology, cardiovascular research institute, university of california, san francisco, ca 94143, usa email.
In ocular epithelia, fluid transport generally involves secondary active chloride transport, which creates the osmotic gradient to drive transepithelial water transport. Mar 18, 2020 diabetes insipidus di is defined as the passage of large volumes 3 l24 hr of dilute urine as arginine vasopressin avp nephrogenic di, charac. Moreover, these studies predicted that additional members of the aquaporin family would be identified, and that these aquaporins participate in other important clinical disorders predicted by the sites where the proteins are expressed. Using immunoprecipitation studies, zhang and verkman 112 showed. Aquaporins as diagnostic and therapeutic targets in cancer core. There are at least 10 aquaporins in mammals and many more in plants, amphibians and lower organisms. Since the discovery of the aquaporins ten years ago, researchers around the world have sought to learn how these proteins work. Aquaporin 4 and neuromyelitis optica pubmed central pmc.
Water moves through cells in an organized way, most rapidly in tissues that have aquaporin water channels. Aquaporins aqps are integral membrane proteins that enable the movement of water and other small solutes across biological membranes. Department of medical biology, amsterdam university medical centers. Verkman departments of medicine and physiology, cardiovascular research institute, room 1246, box 0521 university of california san francisco, san francisco, ca 941430521, usa email. Aquaporins are exquisitely selective for the transport of water even repelling hydronium ions h 3 o. Aquaporins in clinical medicine europe pmc article europe pmc. This polarized expression of aqp4 may result from intracellular interactions between this channel and. Hara m, ma t, verkman as 2002 selectively reduced glycerol in skin of aquaporin3deficient mice may account for impaired skin hydration, elasticity, and barrier recovery. The aquaporins aqp are a family of homologous water. To investigate the effect of abnormal savda munziq asm on the pulmonary function and expression of lungspecific aquaporins in the rat model of chronic obstructive pulmonary disease with abnormal savda syndrome asscopd.
At least 10 mammalian aquaporins have been identified, and these are selectively permeated by water aquaporins or water plus glycerol aquaglyceroporins. Neuromyelitis optica is an inflammatory demyelinating disorder of the cns. The discovery of circulating igg1 antibodies against the astrocyte water channel protein aquaporin 4 aqp4 and the evidence that aqp4igg is involved in the development of neuromyelitis optica revolutionised our understanding of the disease. Aquaporins belong to the major intrinsic protein mip superfamily, and have been identified in almost every organism, including vertebrates, invertebrates, plants and single celled organisms, the phylogeny of which has been extensively discussed heymann and engel, 1999, kruse et al. Jul 22, 2004 thus, secondary disorders of aqp2 are of paramount importance to the practice of clinical medicine. They have a similar basic structure, with aquaporin monomers consisting of six transmembrane helical segments and two short helical segments that surround cytoplasmic and. Marples and taehwan kwon and peter agre and mark a. Reduced expression of aquaporins in human intestinal mucosa. Aquaporins are intrinsic membrane proteins characterized by six transmembrane helices that selectively allow water. Saadoun s, papadopoulos mc, watanabe h, yan d, manley gt, verkman as. Phenotype analysis of aquaporinknockout mice has con.
Aquaporins aqps are a family of water channel proteins distributed in various human. Biochimica et biophysica acta bba biomembranes, 17886, pp. They have a similar basic structure, with aquaporin monomers consisting of six transmembrane helical segments and two short helical segments that surround cytoplasmic and extracellular vestibules connected. Aquaporins aqps, also called water channels, were first discovered in 1992 by agre et al. Aquaporin water channels and endothelial cell function. Although aqp4 is widely expressed in the astrocyte cell plasma membrane, it is primarily localized to specific regions, such as astrocyte foot processes 17,30. Aquaporins aqps are a family of water channel proteins distributed in various human tissues, responsible for the transport of small solutes such as glycerol, even gas and ions.
There are mammalian aquaporins, which are widely distributed in specific cell types in many organs and tissues. Evidencebased complementary and alternative medicine. Dissecting the role of aquaporins in renal pathophysiology using transgenic mice. Mice lacking aqp4 have a worse clinical outcome and greater brain water. For many years, scientists assumed that water leaked through the cell membrane, and some water does. Aquaporins as diagnostic and therapeutic targets in cancer.
Hines, in equine internal medicine fourth edition, 2018. Sep 25, 20 reduced water permeability and altered ultrastructure in thin descending limb of henle in aquaporin1 null mice. The other 12 aquaporins can be broadly divided into three families. Aquaporins aqps and the cystic fibrosis transmembrane conductance regulator cftr provide the molecular routes for transport of water and chloride, respectively, through many epithelial tissues. Feb 18, 2012 aquaporins in clinical medicine aquaporins in clinical medicine verkman, a. Schnermann j, chou cl, ma t, traynor t, knepper ma, verkman as. Eighty male rats were randomized into asscopd, copd, and control groups. Agre p, king ls, yasui m, guggino wb, ottersen op, fujiyoshi y, et al. Selectivity, rates of permeation, and gating mechanisms are three properties that characterize channel proteins.
Aquaporins in drug discovery and pharmacotherapy sciencedirect. Aquaporins biology bibliographies cite this for me. There is considerable potential for translating knowledge of aquaporin structure, function and physiology to the clinic. Verkman 0 0 departments of medicine and physiology, 1246 health sciences east tower, university of california, san francisco, ca 941430521, usa with a concentration of 55,000 mm, water is by far the most prevalent molecule in biological systems. The mechanism by which water passes through biological membranes was a matter of debate until the discovery of the aquaporin water channels. Aquaporinlike protein from the ovaries and gut of american. Aquaporinsnew players in cancer biology springerlink.