Resveratrol diminishes bisphenol A-induced oxidative stress through TRPM2 channel in the mouse kidney cortical collecting duct cells

Bisphenol A (BisPH-A) is a latent danger that threatens our health, which we frequently exposure in our modern life (e.g. the widespread use of drinking water in plastic pet bottles). But the BisPH-A induced transient receptor potential melastatin 2 (TRPM2)-mediated oxidative stress and apoptosis in these cells has not been studied yet. Calcium (Ca2+) plays an important role in a versatile intracellular signal transduction that works over a wide range to regulate oxidative stress processes. TRPM2 is activated by oxidative stress and it has emerged as an important Ca2+ signaling mechanism in a variety of cells, contributing many cellular functions including cell death. Resveratrol (RESV), which belongs to the polyphenol group, acts as an antioxidant, eliminating cellular oxidative stress and increasing the body’s resistance to diseases. The current study aimed to elucidate the effect of antioxidant resveratrol on TRPM2-mediated oxidative stress induced by BisPH-A exposure in the mouse kidney cortical collecting duct cells (mpkCCDcl4). The cells were divided into four groups as control, resveratrol (50 µM for 24 h), BisPH-A (100 µM for 24 h) and BisPH-A + RESV. Intracellular free Ca2+ concentrations and TRPM2 channel currents were high in BisPH-A treated cells, but decreased with resveratrol treatment. In addition, BisPH-A induced mitochondrial membrane depolarization, reactive oxygen species (ROS), caspase 3, caspase 9 and apoptosis values were decreased by the resveratrol treatment. In conclusion, resveratrol protected cells from BisPH-A induced oxidative damage. In this study, we showed that TRPM2 channel mediates this protective effect of resveratrol. © 2020 Informa UK Limited, trading as Taylor & Francis Group

Albumin evokes Ca 2+ -induced cell oxidative stress and apoptosis through TRPM2 channel in renal collecting duct cells reduced by curcumin

In proteinuric nephropathies of chronic kidney disease, the epithelial cells of the nephron including the collecting duct are exposed to high concentrations of luminal albumin. Albumin is taken up from collecting duct cells by endocytosis causing excessive reactive oxygen species (ROS) production and a proinflammatory response. Curcumin used in the traditional medicine possesses anti-inflammatory and antioxidant effects. ROS and ADP-ribose (ADPR) activate the cation channel TRPM2. We hypothesize, that albumin-induced cell stress and proinflammatory response are mediated by Ca2+ and can be reduced by curcumin. The cortical collecting duct (CCD) cells mpkCCDc14 exhibit spontaneous and inducible Ca2+ oscillations, which can be blocked by pre-treatment with curcumin. Curcumin accumulates in plasma membrane and intracellular vesicles, where it interferes with TRPM2 and decreases the influx of Ca2+. Albumin reduces cell viability and increases apoptosis, NF-κB activation, and mitochondrial membrane depolarization via Ca2+-dependent signaling, which results in increased ROS production. Albumin-induced cell stress is diminished by the inhibition of TRPM2 after administration of curcumin and ADPR (PARP1) inhibitors. Curcumin did not reduce the Ca2+ elevation induced by thapsigargin in Ca2+-free medium, but it reduced the function of store-operated Ca2+ channels and ATP-evoked Ca2+ response. In conclusion, albumin-induced oxidative stress is mediated by Ca2+-dependent signaling via TRPM2 and leads to cell damage and a proinflammatory response, strengthening the role of CCD cells in the progression of chronic kidney disease

Menthol evokes Ca2+ signals and induces oxidative stress independently of the presence of TRPM8 (menthol) receptor in cancer cells

Menthol is a naturally occurring monoterpene alcohol possessing remarkable biological properties including antipruritic, analgesic, antiseptic, anti-inflammatory and cooling effects. Here, we examined the menthol-evoked Ca2+ signals in breast and prostate cancer cell lines. The effect of menthol (50–500µM) was predicted to be mediated by the transient receptor potential ion channel melastatin subtype 8 (TRPM8). However, the intensity of menthol-evoked Ca2+ signals did not correlate with the expression levels of TRPM8 in breast and prostate cancer cells indicating a TRPM8-independent signaling pathway. Menthol-evoked Ca2+ signals were analyzed in detail in Du 145 prostate cancer cells, as well as in CRISPR/Cas9 TRPM8-knockout Du 145 cells. Menthol (500µM) induced Ca2+ oscillations in both cell lines, thus independent of TRPM8, which were however dependent on the production of inositol trisphosphate. Results based on pharmacological tools point to an involvement of the purinergic pathway in menthol-evoked Ca2+ responses. Finally, menthol (50–500µM) decreased cell viability and induced oxidative stress independently of the presence of TRPM8 channels, despite that temperature-evoked TRPM8-mediated inward currents were significantly decreased in TRPM8-knockout Du 145 cells compared to wild type Du 145 cells

Recognition of Human Emotions by Machine Learning Method Using Turkish Music Stimuli

Music is an audio signal consisting of a wide variety of complex components which vary according to time and frequency. It is widely accepted in the literature that music evokes a wide variety of emotions in the audience. When a person says that the music they are listening to contains sad or happy feelings, this may not reveal the feeling they actually feel. However, according to the emotion felt during listening to music, fluctuations in electrical activity of the brain can more accurately reveal the structure of perceived true emotion. Detecting human emotions using brain signals has been the subject of current research in many areas. In this study, the problem of detection human emotions while listening to music has been discussed. Experiments are carried out both on our own dataset and on the DEAP dataset, which is widely used in the literature. Different types of Turkish music’s were played to the participants. By examining the electrical waves that occur in their brain's surface, happy, sad, relaxing and angry mood states were recognized. Participants were asked to listen to music from different types in a noiseless environment. To classification the emotions, electroencephalography (EEG) signals were saved primarily from different channels. Certain features have been extracted from these signals. Extracted features have been classified using machine learning algorithms for Support Vector Machines (SVM), K nearest neighbor (KNN), and Artificial Neural Networks (ANN). The best accuracy rate was obtained by ANN from algorithms used to train the data set and classify human emotions. According to the results obtained, it was observed that the used method performed well

TRP Channels in Oxidative Stress Signalling

It is well established that the accumulation of high levels of reactive oxygen species (ROS), due to excessive generation of ROS and/or impaired antioxidant capacity of cells, can result in oxidative stress and cause oxidative damage to cells and their functions [...

The role of astrocyte signalling pathways in ageing induced neurodegenerative pathologies

Astrocytes are a group of cells with specific morphological and functional characteristics that vary in different regions of the brain. During postnatal development, astrocytes migrate to the regions of interest in the brain. Astrocytes interact with neurons to protect, support and maintain normal cellular homeostasis during physiological ageing of the central nervous system (CNS), including the brain, spinal cord and retina. Mature astrocytes retain most of the genes expressed in progenitor cells to keep their proliferative potential. In the last few decades, astrocytes have been reported to serve an important role in age-related neurodegenerative diseases.

Editorial: The role of astrocyte signalling pathways in ageing-induced neurodegenerative pathologies

Astrocytes are a group of cells with specific morphological and functional characteristics that vary in different regions of the brain. During postnatal development, astrocytes migrate to the regions of interest in the brain. Astrocytes interact with neurons to protect, support and maintain normal cellular homeostasis during physiological ageing of the central nervous system (CNS), including the brain, spinal cord and retina. Mature astrocytes retain most of the genes expressed in progenitor cells to keep their proliferative potential. In the last few decades, astrocytes have been reported to serve an important role in age-related neurodegenerative diseases.

Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels

There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells. This indicates that MCF7 cells not only express functional TRPV1 channels, but also produce endogenous TRPV1 agonists. We investigated the effects of MRS1477 and capsaicin on cell viability, caspase-3 and -9 activities and reactive oxygen species production in MCF7 cells. The fraction of apoptotic cells was increased after 3 days incubation with capsaicin (10 μM) paralleled by increased reactive oxygen species production and caspase activity. These effects were even more pronounced, when cells were incubated with MRS1477 (2 μM) either alone or together with CAPS (10 μM). Capsazepine, a TRPV1 blocker, inhibited both the effect of capsaicin and MRS1477. Whole-cell patch clamp recordings revealed that capsaicin-evoked TRPV1-mediated current density levels were increased after 3 days incubation with MRS1477 (2 μM). However, the tumor growth in MCF7 tumor-bearing immunodeficient mice was not significantly decreased after treatment with MRS1477 (10 mg/ kg body weight, i.p., injection twice a week). In conclusion, in view of a putative in vivo treatment with MRS1477 or similar compounds further optimization is required