Mosquitoes (Anopheles sinensis), widely geographically distributed in Asia including China, are the primary vector of the malaria parasite Plasmodium vivax and other parasitic diseases such as Malayan filariasis. An. sinensis can survive through low winter temperatures. Aquaporin channels are found in all life forms, where they facilitate environmental adaptation by allowing rapid trans-cellular movement of water (classical aquaporins) or water and solutes such as glycerol (aquaglyceroporins). Here, we identified and characterized 2 aquaporin (AQP) homologs in An. sinensis: AsAQP2 (An. sinensis aquaglyceroporin) and AsAQP4 (An. sinensis aquaporin). When expressed in frog (Xenopus laevis) oocytes, AsAQP2 transported water, glycerol, and urea; AsAQP4 transported only water. Water permeation through AsAQP2 and AsAQP4 was inhibited by mercuric chloride. AsAQP2 expression was slightly higher in adult female mosquitoes than in males, and AsAQP4 expression was significantly higher in adult males. The 2 AsAQPs were highly expressed in Malpighian tubules and midgut. AsAQP2 and AsAQP4 expression was up-regulated by blood feeding compared with sugar feeding. At freezing point (0 °C), the AsAQP4 expression level increased and An. sinensis survival time reduced compared with those at normal temperature (26 °C). At low temperature (8 °C), the AsAQP2 and AsAQP4 expression levels decreased and survival time was significantly longer compared with those at 26 °C. These results suggest that AsAQP2 and AsAQP4 have roles in water homeostasis during blood digestion and in low temperature adaptation of A. sinensis. Together, our results show that the 2 AQPs are important for mosquito diuresis after blood feeding and when exposed to low temperatures.

Antimony (Sb) is a non-essential metalloid that can be taken up by plants from contaminated soils and thus enter the food chain and threaten human health. Boehmeria nivea L. (ramie) is a promising phytoremediation plant for Sb-polluted soils. However, the mechanisms of antimonite (SbIII) and antimonate (SbV) uptake by ramie remain unclear. In this study, a hydroponic system was established to investigate how different substances affect the uptake of SbIII or SbV by ramie, including an energy inhibitor (malonic acid), an aquaglyceroporin inhibitor (silver nitrate), an SbV analog (phosphate-PV), and SbIII analogs (arsenite-AsIII, glycerol, silicic acid-Si, and glucose). The results indicated that ramie primarily transported Sb by increasing the Sb concentration in the bleeding sap, rather than increasing the weight of the bleeding sap. After 16 h of Sb exposure, the absolute amount of transported Sb from the roots to the aboveground parts was 1.90 times higher under SbIII than under SbV. The addition of malonic acid significantly inhibited the uptake of SbV but had limited effects on SbIII, indicating that SbV uptake was energy dependent. PV addition significantly reduced SbV uptake, while the addition of AsIII, glycerol, and Si obviously inhibited SbIII uptake. This suggested that the uptake of SbV might be via low-affinity P transporters and SbIII might use aquaglyceroporins. These findings deepen the understanding of Sb uptake pathways in ramie, contribute to a better comprehension of Sb toxicity mechanisms in ramie, and establish a foundation for identifying the most effective Sb uptake pathways, which could further improve the efficiency of phytoremediation of Sb-polluted soils.

Aquaglyceroporins (AQGPs), including AQP3, AQP7, AQP9, and AQP10, are transmembrane channels that allow small solutes across biological membranes, such as water, glycerol, H2O2, and so on. Increasing evidence suggests that they play critical roles in cancer. Overexpression or knockdown of AQGPs can promote or inhibit cancer cell proliferation, migration, invasion, apoptosis, epithelial-mesenchymal transition and metastasis, and the expression levels of AQGPs are closely linked to the prognosis of cancer patients. Here, we provide a comprehensive and detailed review to discuss the expression patterns of AQGPs in different cancers as well as the relationship between the expression patterns and prognosis. Then, we elaborate the relevance between AQGPs and malignant behaviors in cancer as well as the latent upstream regulators and downstream targets or signaling pathways of AQGPs. Finally, we summarize the potential clinical value in cancer treatment. This review will provide us with new ideas and thoughts for subsequent cancer therapy specifically targeting AQGPs.

Arsenic is a toxic metalloid that enters cells adventitiously via uptake systems for phosphate transporters, aquaglyceroporins (AQPs) or sugar permeases. However, transport of highly toxic methylarsenite (MAs(III)) and relatively nontoxic methylarsenate (MAs(V)) by bacterial AQPs has not been characterized. MAs(V) has a history of use as an herbicide. Here we used whole genome sequence analysis of AQPs in arsenic resistance (ars) operons. The aqp genes are frequently located next to MAs(III) resistance genes such as arsH, which suggests that they could be involved in MAs(III) uptake. Bacterial AQPs encoded by ars operons can be classified into two subgroups. One subgroup includes AqpS from the plant symbiont Sinorhizobium meliloti 1021. Our data suggests that AqpS has a substrate selectivity filter different from that of other bacterial AQPs. Both Escherichia coli GlpF and AqpS conduct MAs(III) efficiently, but GlpF conducts the MAs(V) anion poorly, so E. coli takes up MAs(V) inefficiently. In contrast, AqpS conducts MAs(V) under physiological conditions. A homology model of AqpS indicates that it has a substrate channel with a selectivity filter containing the nonpolar residue Val177 instead of the charged arginine residue found in other AQPs. While the selectivity filter in most AQPs prevents movement of anions, Val177 is predicted to allow movement of the MAs(V) anion through the channel. We propose that AqpS is a component of an MAs(III) resistance pathway in which MAs(III) enters cells of S. meliloti via AqpS, is oxidized by ArsH to MAs(V), which exits the cells via AqpS.

OBJECTIVE: As an important membrane protein, aquaglyceroporin involves liver glycerol metabolism, which can be used to stage liver fibrosis. In this study, we synthesized a novel molecular probe carbon-11-labeled AR ([11C]AR) with aminoglycerol (AR), and evaluated its preclinical performance for liver fibrosis diagnosis by positron emission tomography/computed tomography (PET/CT) imaging in vivo.
METHODS: We developed a fully automatic synthesis procedure for the preparation of [11C]AR by radiolabeling glycerol analogue precursor AR with carbon-11. The liver uptake kinetics of [11C]AR was investigated using a rat model by the PET/CT scanner. The dynamic PET/CT scans were performed between the control group (n = 5) and experimental group (n = 25), which was divided into three subgroups (S1, S2 + S3, S4) based on the stages of liver fibrosis. The regions of interest (ROIs) of 20 pixels were drawn in the liver area on the reconstructed images. One-way analysis of variance and independent sample t test were used to analyze the statistical difference of the maximum standardized uptake value (SUVmax) among the groups at series of scanning time points (20 s, 60 s, 90 s, 150 s, 5 min, 10 min, 20 min and 25 min).
RESULTS: The fully automatic synthesis of [11C]AR was successfully achieved with high synthesis efficiency (above 50%). The uptake of [11C]AR in progressive liver fibrosis tissues was significantly lower than that in healthy livers at all the imaging time points (P < 0.05), especially at early time points (before 10 min p.i.). A cut-off SUVmax value (1.1) at 150 s p.i. was set for discrimination progressive fibrosis from healthy liver. More experimental and healthy rats were tested with this new threshold to evaluate fibrosis situation. The sensitivity of detecting progressive fibrosis with [11C]AR was 100% in the second cohort.
CONCLUSIONS: We demonstrated a new carbon-11-radiolabeled aminoglycerol PET/CT imaging probe [11C]AR for liver fibrosis diagnosis and staging, which may allow potential assessment of liver fibrosis stages in a rapid and noninvasive method.

Arsenic is associated with several adverse health outcomes, and people with diabetes may be more susceptible to arsenic. In this study, we found that arsenic levels in some tissues such as liver, kidney, and heart but not lung of type 1 diabetes mellitus (T1DM) mice were higher than in those of normal mice after a single oral dose of arsenic trioxide for 2 h. However, little is known about the molecular mechanism of the increased tissue uptake of trivalent inorganic arsenic in mice with T1DM. This study aimed to investigate the expression of the mammalian arsenic transporters aquaglyceroporins (AQPs) and glucose transporter 1 (GLUT1) in T1DM mice and compare them with those in normal mice. Results showed that the levels of AQP9 and GLUT1 mRNA and protein were higher in T1DM mouse liver than in the normal one. The levels of AQP7 mRNA and protein were higher in T1DM mouse kidney. In the heart, we observed that the levels of AQP7 and GLUT1 mRNA and protein were higher in T1DM mice, but the levels of AQP9 mRNA and protein in the lung had no significant difference between both mice. These results suggested that T1DM may increase the expression of transporters of trivalent inorganic arsenic and thus increase the arsenic uptake in specific tissues.

BACKGROUND: Anopheles gambiae is the major mosquito vector for Plasmodium falciparum malaria in sub-Saharan Africa, where it survives in stressful climates. Aquaporin water channels are expressed in all life forms, where they provide environmental adaptation by conferring rapid trans-cellular movement of water (classical aquaporins) or water plus glycerol (aquaglyceroporins). Here, we report an aquaglyceroporin homolog in A. gambiae, AgAQP3 (A. gambiae aquaglyceroporin 3).
RESULTS: Despite atypical pore-lining amino acids, AgAQP3 is permeated by water, glycerol and urea, and is not significantly inhibited by 1 mM HgCl2 . AgAQP3 is expressed more heavily in male mosquitoes, yet adult female A. gambiae abundantly express AgAQP3 in Malpighian tubules and gut where large amounts of fluid exchange occur during blood meal digestion, water and nutrient absorption and waste secretion. Reducing expression of AgAQP3 by RNA interference reduces median mosquito survival at 39°C. After an infectious blood meal, mosquitoes with depleted AgAQP3 expression exhibit fewer P. falciparum oocysts in the midgut compared to control mosquitoes.
CONCLUSIONS: Our studies reveal critical contributions of AgAQP3 to A. gambiae heat tolerance and P. falciparum development in vivo.
CONCLUSIONS: This study indicates that AgAQP3 may be a major factor explaining why A. gambiae is an important malaria vector mosquito in sub-Saharan Africa, and may be a potential target for novel malaria control strategies.