Phospholipse c inhibitor, u73122, stimulates release of hsp-70 stress protein from A431 human carcinoma cells

BACKGROUND: Accumulating evidences suggest that Hsp 70, the inducible component of Hsp70 family, might release from a living cell. Here we show that a pharmacological inhibitor of phospholipase C activity U73122 caused a 2–4 fold reduction of an intracellular level of Hsp70 in A431 human carcinoma cells. RESULTS: A depletion of Hsp70 under U73122 was a result of the protein release since it was detected in cell culture medium, as was established by immunoprecipitation and precipitation with ATP-agarose. The reduction of Hsp70 level was specifically attributed to the inhibition of PLC, since the non-active inhibitor, U73343, had no effect on Hsp70 level. The PLC-dependent decrease of Hsp70 intracellular level was accompanied by the enhanced sensitivity of A431 cells to the apoptogenic effect of hydrogen peroxide. Here for the first time we demonstrated one of the possibilities for a cell to export Hsp70 in PLC-dependent manner. CONCLUSION: From our data we suggest that phospholipase C inhibition is one of the possible mechanisms of Hsp70 release from cells

The STIM1/2-Regulated Calcium Homeostasis Is Impaired in Hippocampal Neurons of the 5xFAD Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of age-related dementia. Neuronal calcium homeostasis impairment may contribute to AD. Here we demonstrated that voltage-gated calcium (VGC) entry and store-operated calcium (SOC) entry regulated by calcium sensors of intracellular calcium stores STIM proteins are affected in hippocampal neurons of the 5xFAD transgenic mouse model. We observed excessive SOC entry in 5xFAD mouse neurons, mediated by STIM1 and STIM2 proteins with increased STIM1 contribution. There were no significant changes in cytoplasmic calcium level, endoplasmic reticulum (ER) bulk calcium levels, or expression levels of STIM1 or STIM2 proteins. The potent inhibitor BTP-2 and the FDA-approved drug leflunomide reduced SOC entry in 5xFAD neurons. In turn, excessive voltage-gated calcium entry was sensitive to the inhibitor of L-type calcium channels nifedipine but not to the T-type channels inhibitor ML218. Interestingly, the depolarization-induced calcium entry mediated by VGC channels in 5xFAD neurons was dependent on STIM2 but not STIM1 protein in cells with replete Ca2+ stores. The result gives new evidence on the VGC channel modulation by STIM2. Overall, the data demonstrate the changes in calcium signaling of hippocampal neurons of the AD mouse model, which precede amyloid plaque accumulation or other signs of pathology manifestation

Study of polylactic acid electret by dielectric spectroscopy

© 2016 AIP Publishing LLC.Correlation between the electret and dielectric properties of the PLA samples charged at different conditions was studied. Electret state of polylactic acid characterized by macromolecule segmental orientation is reflected on dielectric spectra that were used to calculate relaxation energy

Study of electret state in polylactic acid with nanosized filler by dielectric spectroscopy

© 2016 Author(s).Dielectric spectroscopy method was implemented to study electret state in both polylactic acid and its composites with nano-sized aerosil. Two components of the activation energy for the dielectric relaxation process, related to glass transition and segmental mobility of the macromolecules, were obtained. The lifetime and thermal stability of the electret state increased due to the addition of the filler. The optimal SiO2 content for negative corona electrets was found to be 4 wt. %

GAPDH binders as potential drugs for the therapy of polyglutamine diseases: Design of a new screening assay

AbstractProteins with long polyglutamine repeats form a complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which enhances aggregation and cytotoxicity in models of Huntington disease. The aim of this study was to develop a novel assay for the screening of anti-aggregation compounds with a focus on the aggregation-promoting capacity of GAPDH. The assay includes a pure Q58 polyglutamine fragment, GAPDH, and a transglutaminase that links the two proteins. The feasibility of the new assay was verified using two GAPDH binders, hydroxynonenal and −(−)deprenyl, and the benzothiazole derivative PGL-135 which exhibits anti-aggregation effect. All three substances were shown to reduce aggregation and cytotoxicity in the cell and in the fly model of Spinocerebellar ataxia

Pyrrolylquinoxaline-2-one derivative as a potent therapeutic factor for brain trauma rehabilitation

Traumatic brain injury (TBI) often causes massive brain cell death accompanied by the accumulation of toxic factors in interstitial and cerebrospinal fluids. The persistence of the damaged brain area is not transient and may occur within days and weeks. Chaperone Hsp70 is known for its cytoprotective and antiapoptotic activity, and thus, a therapeutic approach based on chemically induced Hsp70 expression may become a promising approach to lower post-traumatic complications. To simulate the processes of secondary damage, we used an animal model of TBI and a cell model based on the cultivation of target cells in the presence of cerebrospinal fluid (CSF) from injured rats. Here we present a novel low molecular weight substance, PQ-29, which induces the synthesis of Hsp70 and empowers the resistance of rat C6 glioma cells to the cytotoxic effect of rat cerebrospinal fluid taken from rats subjected to TBI. In an animal model of TBI, PQ-29 elevated the Hsp70 level in brain cells and significantly slowed the process of the apoptosis in acceptor cells in response to cerebrospinal fluid action. The compound was also shown to rescue the motor function of traumatized rats, thus proving its potential application in rehabilitation therapy after TBI. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Ministry of Education and Science of the Russian Federation, Minobrnauka: 0124-2019-002Russian Foundation for Basic Research, RFBR: 20-33-70102Russian Science Foundation, RSF: 18-74-10087Funding: This research was funded by Russian Science Foundation, research project #18-74-10087 (V.F.L., E.A.D., M.A.M., E.R.M.), Russian Foundation for Basic Research, research project #20-33-70102 (I.A.U., O.N.C., V.N.C, M.?.T., I.V.G.), and by The Ministry of Education and Science of Russian Federation № 0124-2019-002 (R.V.S., N.D.A., B.A.M.)

COMPOSITE ELECTRET MATERIAL BASED ON POLYLACTIC ACID AND MONTOMORILLONITE

Electret properties of the composite material based on polylactic acid and montmorillonite were studied. Addition of montmorillonite improved time stability of the charge in the polymer

Investigation of Packaging Films with Electret Effect

The possibility of using electret polymeric materials for milk packaging has been investigated. It is noted that the electric field of the packaging material can inhibit the growth of bacteria harmful to dairy production

Dataset of NMR-Spectra Pyrrolyl- and Indolylazines and Evidence of Their Ability to Induce Heat Shock Genes Expression in Human Neurons

These data are related to our previous paper “Synthesis and approbation of new neuroprotective chemicals of pyrrolyl- and indolylazine classes in a cell model of Alzheimer's disease” (Dutysheva et al., 2021), in which we demonstrate neuroprotective abilities of pyrrolyl- and indolylazines in a cell model of Alzheimer's disease. Using a novel procedure of photocatalysis we have synthesized a group of new compounds. The current article presents nuclear magnetic resonance spectra including heteronuclear single quantum coherence spectra of chemicals synthesized by us. The effect of new compounds have on heat shock proteins genes expression in reprogrammed human neurons are presented. We also presented data that verify neuronal phenotype of reprogrammed cells. © 2021Funding: This work was supported by the Russian Foundation for Basic Research [Grant No. 20–33–70102], and by the Russian Science Foundation [grant number 18–74–10087]