Chapter Five - Aquaporins in health and disease
Introduction
Aquaporins (AQPs) constitute a family of proteins with channel functions, which are located in the plasma cell membrane and mediate the water transport [1], [2], [3]. A total of 13 proteins (AQP1–12Α, Β) are included in the AQP family in Homo sapiens [1]. Although the majority of the AQPs facilitate the water translocation, certain AQPs (AQP3, AQP7, AQP9) also play a significant role in glycerol transportation, thus being referred as aquaglyceroporins [4]. In the same context, all AQPs have been associated with additional attributes that will be further assessed in the following paragraphs. For instance, certain AQPs mediate the translocation of ions, despite their primary function of water transfer [5], [6].
The structure of the AQPs contains six transmembrane α-helices, embedded in the cell membrane as homotetramers [7]. Each of the four monomers contains a unique pore, functioning like a water channel [7], with the amino- and carboxyl-terminal regions facing toward the interior surface of the cell membrane [8], [9]. There are five biochemical regions (A–E) located among the α-helices which loop through the cell membrane. Two (B and E) of these regions are hydrophobic, containing a distinct asparagine-proline-alanine pattern (NPA motif) [10]. This complex biochemical structure enables the AQPs to increase the water permeability through the plasma cell membrane [11].
In this chapter, we will discuss the functions of AQPs in different biologic contexts, along with uncovering their role and potential in health and disease.
Section snippets
The protein family of aquaporins
The uncovering of the potential existence of AQPs originated with the observation of the functionality of the cell membrane as an osmotic sieve that enables the water transfer [12], which was sensitive to organomercury elements, thus suggesting that the water translocation was channel-depended [13]. Based on these findings, newer articles demonstrated certain 28 kDa channel-forming proteins anchored in the cell membrane [14] which augmented the osmotically driven water transfer through cell
Aquaporins in respiratory diseases
Among the members of the AQP superfamily, only AQP1, AQP3, AQP4, and AQP5 are expressed in the lungs. AQP1 is found in cell membranes of endothelial cells along the airway tract [40], [41], [42], [43], [44]. Moreover, AQP3, AQP4, and AQP5 are mainly expressed in the lateral membranes of the basal or epithelial cells of the nasal surfaces [45], [46], trachea, bronchi, and bronchiole, along with the alveolar epithelial type I and II cells [47], [48], [49]. According to findings from experiments
Aquaporins in gastrointestinal malignancies
There is increasing evidence regarding the implication of AQPs in the pathobiology of various malignancies of the gastrointestinal tract. Herein, we will summarize their role in the biology of esophageal, gastric, colorectal, hepatic and pancreatic malignancies.
Aquaporins in renal diseases
Eight out of the totally 13 AQPs are expressed in kidneys, including AQP1, AQP2, AQP3, AQP4, AQP5, AQP6, AQP7, and AQP11, and they are implicated in various physiologic functions, such as the urine concentration, water reabsorption and metabolism [100], [101]. AQP1 is a selective water-permeable channel protein that is located in the plasma membrane of the proximal tubule, descending limb of the Henle tubule, and descending vasa recta [102]. AQP2 regulates the urine concentration by increasing
Aquaporins in neurosurgical diseases
Water homeostasis in the central nervous system (CNS) is of paramount physiologic and clinical importance because 80% weight of the brain is water [116]. Water transport is linked to the production and drainage of cerebrospinal fluid, cell volume regulation, and the regulation of the extracellular space [117], [118]. In CNS disorders, water transport plays an important role in cerebral edema, which may lead to neurologic dysfunction, deficits including cerebral herniation and death due to a
Aquaporins in female-specific malignancies
Recently, there is growing evidence unveiling the role of AQPs in gynecologic cancers. Generally, AQPs are upregulated in female-specific malignancies [139]. Herein, we discuss the role of AQPs in the most common gynecologic malignancies.
Summary and future perspectives
Taking everything into consideration, the AQPs play a pivotal role in both human health and disease. Nonetheless, it is necessary to further evaluate the mechanism behind the transmembrane fluid transport, along with the intracellular junctions, in order to fully understand their biological role in normal and pathologic conditions. The evidence that was summarized and presented in this chapter uncovered the potential of incorporating certain AQPs as biomarkers or prognostic markers in various
Conflict of interest
The participating authors declare no conflicts of interest.
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