Human aquaporin-11 guarantees efficient transport of H2O2 across the endoplasmic reticulum membrane

Hydrogen peroxide (H2O2) is an essential second intracellular messenger. To reach its targets in the cytosol, H2O2 must cross a membrane, a feat that requires aquaporins (AQP) endowed with 'peroxiporin' activity (AQP3, AQP8, AQP9). Here, we exploit different organelle-targeted H2O2-sensitive probes to show that also AQP11 efficiently conduits H2O2. Unlike other peroxiporins, AQP11 is localized in the endoplasmic reticulum (ER), accumulating partly in mitochondrial-associated ER membranes (MAM). Its downregulation severely perturbs the flux of H2O2 through the ER, but not through the mitochondrial or plasma membranes. These properties make AQP11 a potential regulator of ER redox homeostasis and signaling.This work was supported in part through grants from the Associazione Italiana Ricerca sul Cancro (IG 2016-18824 to R.S.), the Fondazione Cariplo (2015-0591 to R.S.), and the Telethon (GGP15059 to R.S.). A.R. was supported by local funds from the University of Ferrara and the Italian Ministry of Health (GR-2016-02364602). Italian Association for Cancer Research (AIRC, IG-18624), Telethon (GGP11139B), and local funds from the University of Ferrara to P.P

Discomfort relief after paracetamol administration in febrile children admitted to a third level paediatric emergency department

Backgroundinternational guidelines recommend treating fever in children not at a predefined body temperature limit but based on the presence of discomfort. However few studies evaluated discomfort relief after administration of antipyretics in children.MethodsBetween 1st January and 30th September 2021 a single-center prospective observational study was performed in febrile children consecutively admitted to a pediatric emergency department and treated with paracetamol orally. For each child, body temperature, presence and severity of discomfort, defined using a previously published semiquantitative likert scale, were evaluated at baseline and 60 min after administration of paracetamol, and differences were analyzed.Results172 children (males: 91/172; 52.9%; median age: 41.7 months) were included. Significant reductions in body temperature (median body temperature at T0: 38.9 °C; IQR: 38.3–39.4, median body temperature at T60: 36.9 °C; IQR: 36.4–37.5; P Conclusionsparacetamol in febrile children is associated not only with significantly reduction in body temperature but also with discomfort relief.</p

A persulfidation-based mechanism controls aquaporin-8 conductance

Upon engagement of tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases release H2O2 in the extracellular space. We reported previously that aquaporin-8 (AQP8) transports H2O2 across the plasma membrane and is reversibly gated during cell stress, modulating signal strength and duration. We show that AQP8 gating is mediated by persulfidation of cysteine 53 (C53). Treatment with H2S is sufficient to block H2O2 entry in unstressed cells. Silencing cystathionine beta-synthase (CBS) prevents closure, suggesting that this enzyme is the main source of H2S. Molecular modeling indicates that C53 persulfidation displaces a nearby histidine located in the narrowest part of the channel. We propose that H2O2 molecules transported through AQP8 sulfenylate C53, making it susceptible to H2S produced by CBS. This mechanism tunes H2O2 transport and may control signaling and limit oxidative stress.This work was supported in part through grants from the Associazione Italiana Ricerca sul Cancro (IG 2016-18824 to R.S. and IG 2016-15434 to A.R.), the Fondazione Cariplo (2015-0591 to R.S.), the Ministero della Salute (PE-2011-02352286 to R.S. and RF-2013-02354880 to G.M.), the Telethon (GGP15059 to R.S.), and the "Cinque per mille"; (to A.R.). G.P.B. was supported by an Emmy Noether grant 1668/1-1 from the Deutsche Forschungsgemeinschaft

In Vitro and In Vivo Human Herpesvirus 8 Infection of Placenta

Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women

Fully Integrated, 406 μA, 5°/hr, Full Digital Output Lissajous Frequency-Modulated Gyroscope

In this paper, a complete system of a frequency-modulated gyroscope with digital output for future low-power, high-stability, and wide full-scale applications is presented. The system includes the microelectromechanical transducer, two analog oscillators, two mixed-signal frequency to digital converters, and a fundamental mixed-signal block for the real-time extraction and digitization of the demodulation phase reference. With an overall consumption of 406 uA, the system has a 90 dB dynamic range on a 50 Hz bandwidth, with a 5°/hr stability after 20-min observation interval, and a scale-factor drift coefficient of 20 ppm/K only

Stress Regulates Aquaporin-8 Permeability to Impact Cell Growth and Survival

Aquaporin-8 (AQP8) allows the bidirectional transport of water and hydrogen peroxide across biological membranes. Depending on its concentration, H2O2 exerts opposite roles, amplifying growth factor signaling in physiological conditions, but causing severe cell damage when in excess. Thus, H2O2 permeability is likely to be tightly controlled in living cells. AIMS: In this study, we investigated whether and how the transport of H2O2 through plasma membrane AQP8 is regulated, particularly during cell stress. RESULTS: We show that diverse cellular stress conditions, including heat, hypoxia, and ER stress, reversibly inhibit the permeability of AQP8 to H2O2 and water. Preventing the accumulation of intracellular reactive oxygen species (ROS) during stress counteracts AQP8 blockade. Once inhibition is established, AQP8-dependent transport can be rescued by reducing agents. Neither H2O2 nor water transport is impaired in stressed cells expressing a mutant AQP8, in which cysteine 53 had been replaced by serine. Cells expressing this mutant are more resistant to stress-, drug-, and radiation-induced growth arrest and death. INNOVATION AND CONCLUSION: The control of AQP8-mediated H2O2 transport provides a novel mechanism to regulate cell signaling and survival during stress