Mini Review: Forensic Value of Aquaporines

Forensic pathologists are routinely confronted with unclear causes of death or findings. In some scenarios, it can be difficult to answer the specific questions posed by criminal investigators or prosecutors. Such scenarios may include questions about wound vitality or causes of death when typical or landmark findings are difficult to find. In addition to the usual subsequent examinations to clarify unclear causes of death or special questions, immunohistochemical analysis has become increasingly important since its establishment in the early 40s of the 20th century. Since then, numerous studies have been conducted to determine the usefulness and significance of immunohistochemical investigations on various structures and proteins. These proteins include, for example, aquaporins, which belong to the family of water channels. They enable the transport of water and of small molecules, such as glycerol, through biological channels and so far, 13 classes of aquaporins could have been identified in vertebrates. The classic aquaporin channels 1, 2, 4 and 5 are only permeable to water. The aquaporin channels 3, 7, 9, and 10 are also called aquaglycerolporins since they can also transport glycerol. This mini review discusses the immunohistochemical research on aquaporins, their range of applications, and respective forensic importance, their current limitations, and possible further implementations in the future.

Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis

Aquaporin channels facilitate bidirectional water flow in all cells and tissues. AQP4 is highly expressed in astrocytes. In the CNS, it is enriched in astrocyte endfeet, at synapses, and at the glia limitans, where it mediates water exchange across the blood-spinal cord and blood-brain barriers (BSCB/BBB), and controls cell volume, extracellular space volume, and astrocyte migration. Perivascular enrichment of AQP4 at the BSCB/BBB suggests a role in glymphatic function. Recently, we have demonstrated that AQP4 localization is also dynamically regulated at the subcellular level, affecting membrane water permeability. Ageing, cerebrovascular disease, traumatic CNS injury, and sleep disruption are established and emerging risk factors in developing neurodegeneration, and in animal models of each, impairment of glymphatic function is associated with changes in perivascular AQP4 localization. CNS oedema is caused by passive water influx through AQP4 in response to osmotic imbalances. We have demonstrated that reducing dynamic relocalization of AQP4 to the BSCB/BBB reduces CNS oedema, and accelerates functional recovery in rodent models. Given the difficulties in developing pore-blocking AQP4 inhibitors, targeting AQP4 subcellular localization opens up new treatment avenues for CNS oedema, neurovascular and neurodegenerative diseases, and provides a framework to address fundamental questions about water homeostasis in health and disease.

Aquaporin 1 and 3 as local vitality markers in mechanical and thermal skin injuries

Assessment of the vitality of an injury is one of to the main tasks in daily forensic casework. Aquaporins belong to the family of water channels. They enable the transport of water and of small molecules like glycerol through biological channels. So far, 13 classes of aquaporins are identified in vertebrates. The classical aquaporin channels 1, 2 and 4 are only permeable for water. The aquaporin channels 3, 7, 9 and 10 are also called aquaglycerolporins since they can also transport glycerol. Aquaporin 3 is expressed in epidermal keratinocytes. In the present investigation, the aquaporin 1 and 3 expression in mechanically and thermally damaged skin is investigated by immunohistochemistry. The study collective comprises 30 cases (63.3% male and 36.7% female) with an age range between 19 and 95 years (mean value 54.6 years). The skin injury comprises different kinds of blunt force, sharp force, strangulation marks, thermal injury, gunshot wounds and frost erythema. In all kinds of mechanical and trauma injury, an increased expression of aquaporin 3 in the keratinocytes of the epidermis was found. There is no correlation of the aquaporin 3 expression with age, sex, body mass index, duration of agonal period and postmortem interval. Concerning aquaporin 1, there were no differences between injured and uninjured skin. Aquaporin 3 is independently from the kind of skin injury and appears to be a valuable immunohistochemical parameter of vitality.

Aquaporin-like water transport in nanoporous crystalline layered carbon nitride

Designing next-generation fuel cell and filtration devices requires the development of nanoporous materials that allow rapid and reversible uptake and directed transport of water molecules. Here, we combine neutron spectroscopy and first-principles calculations to demonstrate rapid transport of molecular H2O through nanometer-sized voids ordered within the layers of crystalline carbon nitride with a polytriazine imide structure. The transport mechanism involves a sequence of molecular orientation reversals directed by hydrogen-bonding interactions as the neutral molecules traverse the interlayer gap and pass through the intralayer voids that show similarities with the transport of water through transmembrane aquaporin channels in biological systems. The results suggest that nanoporous layered carbon nitrides can be useful for developing high-performance membranes.

Influences of electric fields on the operation of Aqy1 aquaporin channels: a molecular dynamics study

The effects of application of external electric field on the dynamics of water molecules inside an Aquaporin channel, embedded within a stochastically fluctuating membrane, was modeled by means of the application of the molecular dynamics (MD) simulation method.

Nephrogenic diabetes insipidus in a 15-year-old Hispanic female with a novel AQP2 mutation

Nephrogenic diabetes insipidus (NDI) is a rare inherited disorder most often caused by mutations in the arginine-vasopressin receptors or aquaporin channels, which subsequently impairs the water reabsorption in the kidney. This case report describes a 15-year-old female diagnosed with NDI after an acute gastroenteritis and multiple fluid boluses leading to intractable emesis. Gene testing reveals our patient is compound heterozygous for novel AQP2 gene mutations with a cytosine-to-thymine substitution at nucleotide position 277 and adenine-to-cytosine substitution at nucleotide position 659. Therefore, we report a novel AQP2 gene mutation in an adolescent patient which is outside the common age for diagnosis.

Aquaporin Channels in the Heart—Physiology and Pathophysiology

Mammalian aquaporins (AQPs) are transmembrane channels expressed in a large variety of cells and tissues throughout the body. They are known as water channels, but they also facilitate the transport of small solutes, gasses, and monovalent cations. To date, 13 different AQPs, encoded by the genes AQP0–AQP12, have been identified in mammals, which regulate various important biological functions in kidney, brain, lung, digestive system, eye, and skin. Consequently, dysfunction of AQPs is involved in a wide variety of disorders. AQPs are also present in the heart, even with a specific distribution pattern in cardiomyocytes, but whether their presence is essential for proper (electro)physiological cardiac function has not intensively been studied. This review summarizes recent findings and highlights the involvement of AQPs in normal and pathological cardiac function. We conclude that AQPs are at least implicated in proper cardiac water homeostasis and energy balance as well as heart failure and arsenic cardiotoxicity. However, this review also demonstrates that many effects of cardiac AQPs, especially on excitation-contraction coupling processes, are virtually unexplored.

Aquaporins in cancer development: opportunities for bioinorganic chemistry to contribute novel chemical probes and therapeutic agents

Metal ions and complexes can interfere with the transcellular water flow but also with the cellular transport of glycerol and hydrogen peroxide,viainhibition of the ubiquitous aquaporin channels.