Human Aquaporins: Functional Diversity and Potential Roles in Infectious and Non-infectious Diseases

Aquaporins (AQPs) are integral membrane proteins and found in all living organisms from bacteria to human. AQPs mainly involved in the transmembrane diffusion of water as well as various small solutes in a bidirectional manner are widely distributed in various human tissues. Human contains 13 AQPs (AQP0–AQP12) which are divided into three sub-classes namely orthodox aquaporin (AQP0, 1, 2, 4, 5, 6, and 8), aquaglyceroporin (AQP3, 7, 9, and 10) and super or unorthodox aquaporin (AQP11 and 12) based on their pore selectivity. Human AQPs are functionally diverse, which are involved in wide variety of non-infectious diseases including cancer, renal dysfunction, neurological disorder, epilepsy, skin disease, metabolic syndrome, and even cardiac diseases. However, the association of AQPs with infectious diseases has not been fully evaluated. Several studies have unveiled that AQPs can be regulated by microbial and parasitic infections that suggest their involvement in microbial pathogenesis, inflammation-associated responses and AQP-mediated cell water homeostasis. This review mainly aims to shed light on the involvement of AQPs in infectious and non-infectious diseases and potential AQPs-target modulators. Furthermore, AQP structures, tissue-specific distributions and their physiological relevance, functional diversity and regulations have been discussed. Altogether, this review would be useful for further investigation of AQPs as a potential therapeutic target for treatment of infectious as well as non-infectious diseases.

Swelling-strengthening hydrogels by embedding with deformable nanobarriers

Biological tissues, such as muscle, can increase their mechanical strength after swelling due to the existence of many biological membrane barriers that can regulate the transmembrane transport of water molecules and ions. Oppositely, typical synthetic materials show a swelling-weakening behavior, which always suffers from a sharp decline in mechanical strength after swelling, because of the dilution of the network. Here, we describe a swelling-strengthening phenomenon of polymer materials achieved by a bioinspired strategy. Liposomal membrane nanobarriers are covalently embedded in a crosslinked network to regulate transmembrane transport. After swelling, the stretched network deforms the liposomes and subsequently initiates the transmembrane diffusion of the encapsulated molecules that can trigger the formation of a new network from the preloaded precursor. Thanks to the tough nature of the double-network structure, the swelling-strengthening phenomenon is achieved to polymer hydrogels successfully. Swelling-triggered self-strengthening enables the development of various dynamic materials.

Sustainable Growth and Synchronization in Protocell Models

The growth of a population of protocells requires that the two key processes of replication of the protogenetic material and reproduction of the whole protocell take place at the same rate. While in many ODE-based models such synchronization spontaneously develops, this does not happen in the important case of quadratic growth terms. Here we show that spontaneous synchronization can be recovered (i) by requiring that the transmembrane diffusion of precursors takes place at a finite rate, or (ii) by introducing a finite lifetime of the molecular complexes. We then consider reaction networks that grow by the addition of newly synthesized chemicals in a binary polymer model, and analyze their behaviors in growing and dividing protocells, thereby confirming the importance of (i) and (ii) for synchronization. We describe some interesting phenomena (like long-term oscillations of duplication times) and show that the presence of food-generated autocatalytic cycles is not sufficient to guarantee synchronization: in the case of cycles with a complex structure, it is often observed that only some subcycles survive and synchronize, while others die out. This shows the importance of truly dynamic models that can uncover effects that cannot be detected by static graph theoretical analyses.

Ladderane phospholipids form a densely packed membrane with normal hydrazine and anomalously low proton/hydroxide permeability

Ladderane lipids are unique to anaerobic ammonium-oxidizing (anammox) bacteria and are enriched in the membrane of the anammoxosome, an organelle thought to compartmentalize the anammox process, which involves the toxic intermediate hydrazine (N2H4). Due to the slow growth rate of anammox bacteria and difficulty of isolating pure ladderane lipids, experimental evidence of the biological function of ladderanes is lacking. We have synthesized two natural and one unnatural ladderane phosphatidylcholine lipids and compared their thermotropic properties in self-assembled bilayers to distinguish between [3]- and [5]-ladderane function. We developed a hydrazine transmembrane diffusion assay using a water-soluble derivative of a hydrazine sensor and determined that ladderane membranes are as permeable to hydrazine as straight-chain lipid bilayers. However, pH equilibration across ladderane membranes occurs 5–10 times more slowly than across straight-chain lipid membranes. Langmuir monolayer analysis and the rates of fluorescence recovery after photobleaching suggest that dense ladderane packing may preclude formation of proton/hydroxide-conducting water wires. These data support the hypothesis that ladderanes prevent the breakdown of the proton motive force rather than blocking hydrazine transmembrane diffusion in anammox bacteria.

Channel-mediated lactic acid transport: a novel function for aquaglyceroporins in bacteria

MIPs (major intrinsic proteins), also known as aquaporins, are membrane proteins that channel water and/or uncharged solutes across membranes in all kingdoms of life. Considering the enormous number of different bacteria on earth, functional information on bacterial MIPs is scarce. In the present study, six MIPs [glpF1 (glycerol facilitator 1)–glpF6] were identified in the genome of the Gram-positive lactic acid bacterium Lactobacillus plantarum. Heterologous expression in Xenopus laevis oocytes revealed that GlpF2, GlpF3 and GlpF4 each facilitated the transmembrane diffusion of water, dihydroxyacetone and glycerol. As several lactic acid bacteria have GlpFs in their lactate racemization operon (GlpF1/F4 phylogenetic group), their ability to transport this organic acid was tested. Both GlpF1 and GlpF4 facilitated the diffusion of D/L-lactic acid. Deletion of glpF1 and/or glpF4 in Lb. plantarum showed that both genes were involved in the racemization of lactic acid and, in addition, the double glpF1 glpF4 mutant showed a growth delay under conditions of mild lactic acid stress. This provides further evidence that GlpFs contribute to lactic acid metabolism in this species. This lactic acid transport capacity was shown to be conserved in the GlpF1/F4 group of Lactobacillales. In conclusion, we have functionally analysed the largest set of bacterial MIPs and demonstrated that the lactic acid membrane permeability of bacteria can be regulated by aquaglyceroporins.

COMPARATIVE ASSESSMENT OF TOPICAL FORMULATIONS BY PERFORMING TRANSMEMBRANE DIFFUSION AND PERMEATION USING DIFFUSION CELLS

Skin penetration of a drug and the effect of formulation additives can be evaluated by performing diffusion studies. In the present study semisolid cream formulation comprising of bacteriostatic antibiotic of 2 different creams have been compared for the penetration of drug. Based on these in vitro release findings, conclusions were drawn regarding performance characteristics of the pharmaceutically equivalent formulations.