Investigation of cellular morphology and proliferation on patterned electrospun PLA-gelatin mats

Journal of Biological Physics - The morphology and proliferation of eukaryotic cells depend on their microenvironment. When electrospun mats are used as tissue engineering scaffolds, the local...     

Erratum to: Phagocytic Activity of Rat Primary Astrocytes Is Regulated by Insulin and Ganglioside GM1

Journal of Evolutionary Biochemistry and Physiology -     

Arthropod toxins inhibiting Ca2+ and Na+ channels prevent AC‐1001 H3 peptide‐induced apoptosis

Peptide toxins of arthropods are one of the potential sources of bioactive substances. Toxins are able to bind to calcium channels and block them. Ca²⁺ ions play an important role in many cell processes, in particular, in apoptosis. In this work, we study the effect of some arthropod toxins on intracellular processes associated with the induction of apoptosis. Synthetic analogs of U₅‐scytotoxin‐Sth1a, ω‐hexatoxin‐Hv1a, ω‐theraphotoxin‐Hhn2a, and μ‐agatoxin‐Aa1a toxins—inhibitors of calcium L, P, and Q channels and sodium channels were used in the study. Apoptosis was induced by AC‐1001 H3 peptide. We study the effect of toxins on the level of apoptosis, ROS, mitochondrial potential, GSH, and ATP in CHO‐K1 cells. We show that all the tested toxins are able to dose dependently block the induction of apoptosis triggered by AC‐1001 H3 and reduce the level of natural apoptosis in CHO‐K1 cells. Cell incubation with apoptosis inducer AC‐1001 H3 in the presence and absence of toxins causes an increase in the intracellular concentrations of ROS, ATP, and mitochondrial potential and decreases the GSH concentration. The present study reveals the antiapoptotic effect of a number of arthropod peptide toxins. The toxins studied can represent a novel approach used in the treatment of pathologies associated with the activation of apoptotic mechanisms.     

The Content of Vitamin C in the Grape Grown under the Conditions of Southwestern Siberia

Russian Journal of Bioorganic Chemistry - The grape is a highly valuable food stuff owing to the presence of a number of biologically active substances, and vitamins occupy a special place among...     

Results of testing the comparatory method: The curvature of the shell valve frontal section is inappropriate as a systematic character for the freshwater pearl mussel of the genus Margaritifera

This paper continues a discussion on the number of pearl mussel species of the genus Margaritifera in northern Europe. A biometric study of 1711 pearl mussel Margaritifera margaritifera shells from 15 rivers in Russia and Latvia (basins of the White and Baltic seas) has been conducted. All the examined samples fall into two groups: the northern group (with the shells more flattened on average, f. margaritifera) and the southern one (with more convex shells, f. elongata); the boundary between these groups is at 63° N. Analysis of intrapopulation variation has shown that the samples contain individuals that correspond to f. margaritifera, f. elongata, and f. borealis. However, any hiatus between these forms is absent in all the samples, and individuals belonging to two intermediate forms are rather frequent. The hypothesis on the species specificity of the shell valve frontal section has not been confirmed based on examination of large shell samples. The pearl mussels inhabiting rivers of Northern Europe belong to a single species, M. margaritifera.     

Interactive effects of elevated temperature and CO2 levels on metabolism and oxidative stress in two common marine bivalves (Crassostrea virginica and Mercenaria mercenaria)

Marine bivalves such as the hard shell clams Mercenaria mercenaria and eastern oysters Crassostrea virginica are affected by multiple stressors, including fluctuations in temperature and CO₂ levels in estuaries, and these stresses are expected to be exacerbated by ongoing global climate change. Hypercapnia (elevated CO₂ levels) and temperature stress can affect survival, growth and development of marine bivalves, but the cellular mechanisms of these effects are not yet fully understood. In this study, we investigated whether oxidative stress is implicated in cellular responses to elevated temperature and CO₂ levels in marine bivalves. We measured the whole-organism standard metabolic rate (SMR), total antioxidant capacity (TAOC), and levels of oxidative stress biomarkers in the muscle tissues of clams and oysters exposed to different temperatures (22 and 27 °C) and CO₂ levels (the present day conditions of ~ 400 ppm CO₂ and 800 ppm CO₂ predicted by a consensus business-as-usual IPCC emission scenario for the year 2100). SMR was significantly higher and the antioxidant capacity was lower in oysters than in clams. Aerobic metabolism was largely temperature-independent in these two species in the studied temperature range (22–27 °C). However, the combined exposure to elevated temperature and hypercapnia led to elevated SMR in clams indicating elevated costs of basal maintenance. No persistent oxidative stress signal (measured by the levels of protein carbonyls, and protein conjugates with malondialdehyde and 4-hydroxynonenal) was observed during the long-term exposure to moderate warming (+ 5 °C) and hypercapnia (~ 800 ppm CO₂). This indicates that long-term exposure to moderately elevated CO₂ and temperature minimally affects the cellular redox status in these bivalve species and that the earlier observed negative physiological effects of elevated CO₂ and temperature must be explained by other cellular mechanisms.     

An Exposure to the Oxidized DNA Enhances Both Instability of Genome and Survival in Cancer Cells

Background

Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases and acts upon the cells. Response to cfDNA depends on concentrations and levels of the damage within cfDNA. Oxidized extracellular DNA acts as a stress signal and elicits an adaptive response.

Principal Findings

Here we show that oxidized extracellular DNA stimulates the survival of MCF-7 tumor cells. Importantly, in cells exposed to oxidized DNA, the suppression of cell death is accompanied by an increase in the markers of genome instability. Short-term exposure to oxidized DNA results in both single- and double strand DNA breaks. Longer treatments evoke a compensatory response that leads to a decrease in the levels of chromatin fragmentations across cell populations. Exposure to oxidized DNA leads to a decrease in the activity of NRF2 and an increase in the activity of NF-kB and STAT3. A model that describes the role of oxidized DNA released from apoptotic cells in tumor biology is proposed.

Conclusions/Significance

Survival of cells with an unstable genome may substantially augment progression of malignancy. Further studies of the effects of extracellular DNA on malignant and normal cells are warranted.     

Metabolic effects of ganglioside GM1 on PC12 cells in oxidative stress depend on modulation of activity of tyrosine kinase Trk of receptors

There have been obtained evidences that not only GM1, but also other main brain gangliosides (GD1a, GD1b, and GT1b) increase viability of cells of the neuronal line PC12 under action of H₂O₂. By the example of GM1 and GD1a, gangliosides have been shown to produce a protective effect on PC12 cells under conditions of oxidative stress both at micro- and nanomolar concentrations that are physiological concentrations of gangliosides in cerebrospinal fluid. For the first time, GM1 at nanomolar concentrations was shown to decrease the H₂O₂-induced formation of reactive oxygen species (ROS). It was found that in the presence of inhibitor of tyrosine kinase Trk of receptors K-252a, GM1 at concentrations of 10 μM and 10 nM lost its ability to produce such metabolic effects as a decrease of ROS accumulation and of the degree of oxidative inactivation of Na⁺,K⁺-ATPase in PC12 cells, as well as ceased to increase viability of these cells under conditions of oxidative stress. The dependence of protective and metabolic effects of gangliosides GM1 in PC12 cells treated with H₂O₂ on modulation of activity of activity of tyrosine kinase Trk receptors (i.e., from the same signal system) agrees with concept about the essential role of oxidant effect of GM1 in its increase of cell viability.     

Influence of interionic interactions on functional state and blocker binding of voltage-gated potassium channels

A mechanism of ion conduction of a voltage-gated potassium channel KcsA was investigated in full-atomic approximation at a trajectory length of 100 ns using the Lomonosov supercomputer. Methods of molecular dynamics were employed. A structure of the KcsA channel in the open state obtained by X-ray structure analysis (PDB ID 3fb7) was used. Free energy profiles of the KcsA pore occupied with either one or three potassium ions were calculated. It was shown that, under physiological conditions, ions pass through the channel pore cooperatively and the mechanism most probably includes three ions permeating in concert. Interactions of the mammalian voltage-gated channel Kv1.2 with neurotoxin were investigated. It was demonstrated that the effect of interionic interactions on binding of a blocker is rather insufficient.     

Intensive protein synthesis in neurons and phosphorylation of beta-amyloid precursor protein and tau-protein are triggering factors of neuronal amyloidosis and Alzheimer’s disease

Studies of Alzheimer’s disease have become particularly important and attract now much attention of scientists all over the world due to worldwide dissemination of this dangerous disorder. Causes of this pathology still remain unknown, while the final image, originally obtained on microscopic brain sections from patients with this disease more than a hundred years ago, is well familiar to clinicians. This includes deposition of amyloid-β (Aβ) in the brain tissue of senile plaques and fibrils. Many authors believe that the deposition of Aβ provokes secondary neuronal changes, responsible for death of neurons. Other authors associate the death of neurons with hyperphosphorylation of tau-proteins, which form neurofibrillar tangles inside nerve cells and cause their death. Creation of methods of preclinical diagnostics and effective treatment of Alzheimer’s disease requires novel knowledge: on the nature of triggering factors of sporadic forms of Alzheimer’s disease, on cause-effect relationships of phosphorylation of amyloid precursor protein with formation of pathogenic beta-amyloids, on the relationship between these factors underlying tau-protein hyperphosphorylation and neuron death. In this review we have analyzed reports describing increased intensity of protein synthesis in neurons under normal and various stress conditions, possibility of development of energy imbalance of neurons and activation of their protective systems. Phosphorylation and hyperphosphorylation of tau-proteins is also tightly associated with protective mechanisms of cells and with processes of evacuation of phosphates, adenosine monophosphates and pyrophosphates from the region of protein synthesis. Prolonged highly intensive protein synthesis causes overload of protective mechanisms and impairments in concerted metabolic processes. This leads to neuronal dysfunction, transport collapse, and death of neurons.