Mitophagy: Link to cancer development and therapy Kulikov, Andrey V.; Luchkina, Ekaterina A.; Gogvadze, Vladimir ...
Biochemical and biophysical research communications,
01/2017, Volume:
482, Issue:
3
Journal Article
Peer reviewed
Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. Mitophagy is responsible for the removal of ...malfunctioning or damaged mitochondria, which is essential for normal cellular physiology and tissue development. Pathways involved in the regulation of mitophagy, tumorigenesis, and cell death are overlapping in many cases and may be triggered by common upstream signals, which converge at the mitochondria. The failure to properly modulate mitochondrial turnover in response to oncogenic stresses can either stimulate or suppress tumorigenesis. Thus, the analysis of crosstalk among the processes of mitophagy, cell death and tumorigenesis is important for the identification of targets responsible for the stimulation of cell death and selective elimination of cancer cells. In the present review, we analyze the mechanisms of mitophagy regulation, the pathways underlying the utilization of damaged mitochondria, and how intervention with mitophagy can affect tumor cell resistance to treatment.
•Mitophagy, the selective degradation of mitochondria via the autophagic pathway.•Intervention with mitophagy can affect tumor cell resistance to treatment.•A cross-talk between mitophagy, tumorigenesis and cell death exists.
•Hindlimb unloading increased the expression of dopanimergic genes in striatum.•Hippocampus Bcl-xl expression was similar for hindlimb unloading and spaceflight.•Hindlimb unloading did not alter the ...expression of MAOA and 5-HT2A receptor genes.
The study of spaceflight effects on the brain is technically complex concern; complicated by the problem of applying an adequate ground model. The most-widely used experimental model to study the effect of microgravity is the tail-suspension hindlimb unloading model; however, its compliance with the effect of actual spaceflight on the brain is still unclear. We evaluated the effect of one month hindlimb unloading on the expression of genes related to the brain neuroplasticity—brain neutotrophic factors (Gdnf, Cdnf), apoptotic factors (Bcl-xl, Bax), serotonin- and dopaminergic systems (5-HT2A, Maoa, Maob, Th, D1r, Comt), and compared the results with the data obtained on mice that spent one month in spaceflight on Russian biosatellite Bion-M1. No effect of hindlimb unloading was observed on the expression of most genes, which were considered as risk neurogenes for long–term actual spaceflight. The opposite effect of hindlimb unloading and spaceflight was found on the level of mRNA of D1 dopamine receptor and catechol-O-methyltransferase in the striatum. At the same time, the expression of Maob in the midbrain decreased, and the expression of Bcl-xl genes increased in the hippocampus, which corresponds to the effect of spaceflight. However, the hindlimb unloading model failed to reproduce the majority of effects of long-term spaceflight on serotonin-, dopaminergic systems and some apoptotic factors.
For the first time in scientific historiography, with the involvement of previously unknown archival documents, the problem of ensuring freedom of conscience is considered when creating the ...Fundamental Laws on April 23, 1906, which became the first national constitution in force. It is shown that P. A. Kharitonov, A. P. Salomon and Count A. F. Heyden paid attention to this problem, that is, the authors of bureaucratic drafts of new Fundamental Laws, which by December 1905 were prepared for Emperor Nicholas II. The main one turned out to be Kharitonov’s project, considered at a Meeting of the highest ranks of the State Chancellery. In the future, the consolidation of freedom of conscience in the Fundamental Laws was facilitated by the discussion of the draft State Chancellery in the Council of Ministers under the chairmanship of Count S.Y. Witte in March 1906 and the drafting of another draft of Fundamental Laws by Professor O. O. Eichelman at the same time. It is emphasized that the controversy that arose as a result of the April Special Meeting chaired by Nicholas II among his key figures about the limits of freedom of conscience influenced the final version of the corresponding article of the Fundamental Laws established personally by the tsar. It is concluded that this version reflected the conservative-liberal nature of the views shared by the direct participants of the constitutional reform of 1906.
The article examines the reform of the state system of the Russian Empire in 1905—1906, which culminated in the publication of the Fundamental State Laws on April 23, 1906, which summed up ...the previous reforms and became the first domestic constitution. It is noted that at the final stage of the preparation of the Fundamental Laws, there was a problem of integrating the Guardianship Council of the Empress Maria’s Institutions into the new political reality. It is emphasized that legislative measures related to this institution were passed through the Guardianship Council, while according to the new Fundamental Laws, all legislative measures were supposed to go through the State Duma and the State Council. For the first time in scientific historiography, based on previously unknown archival materials, the article examines how representatives of the highest imperial bureaucracy, directly involved in preparing the draft Fundamental Laws, solved this problem. Bureaucratic practices and strategies are analyzed. The author concludes that these representatives acted as defenders of the principles of separation of powers and unity of the legislative path, opposing the inclusion of the Guardianship Council’s legislative nature in the Fundamental Laws. It is shown that a similar position was taken by Nicholas II, which predetermined the exclusion of an article about the Guardianship Council from the final version of the Fundamental Laws.
The article considers the issues related to the principles of building information models from laser method. Optical images of the speckle structures are recorded and subjected to statistical ...processing based on the analysis of the intensity of illumination of discrete points of the studied surfaces. The information thus obtained, saved and interpreted in the article as "phase portrait" of the system under study at a given time. The set thus obtained data is presented in the article as "phase space" of the system under study. On this basis to create an information model that is used in the form of "snapshots" of the state of (ID) in the studied points in time. The parameters of the investigated textures are recorded as statistical data and further formalized.
Display omitted
•The firm uniform ƞ-Al2O3 layer was deposited on the surface of the steel mesh.•Multilayer catalytic units based on metal mesh catalysts were designed and tested.•Fe-based catalysts ...provide high rate of NOx reduction by NH3 without N2O generation.•Addition of WO3 to Pt/Al2O3 catalyst decreases T50 in afterburning of hydrocarbons.•The mesh catalyst provides better light-off performance than the honeycomb catalyst.
The modified Bayer process allows coating of a metal mesh surface with a continuous aluminum hydroxide layer in the phase of bayerite. Subsequent calcination turns the aluminum hydroxide layer into a η-alumina layer. The method provides the uniform thickness of tens of microns for the alumina layer. Layers cracking, clogging of mesh cells are not observed. The alumina layer is formed by needle-shaped particles which coalesce to each other through common facets during crystallization. The alumina layer with high specific surface area is perfectly suitable as a support for various active components. A series of Fe-containing mesh-catalysts was tested in the NOx reduction with NH3. Addition of Ce and W to Fe increases NOx conversion significantly. The FeCeW catalyst provides almost 100% of the NOx conversion at a space velocity of 40,000h−1 in the range of 350–500°C with a negligible quantity of N2O. A series of Pt-containing catalysts was tested in the reaction of afterburning of hydrocarbons. Addition of tungsten oxide to the Pt/Al2O3 catalyst decreases T50 by 60°C. An increase in the number of wire mesh leads to a drop of T50. The mesh-catalyst provides better light-off performance than the honeycomb catalyst.
Herein, we present a systematic study of the photochemical behavior of a set of fullerene compounds bearing various organic addends attached to the fullerene cage. It has been shown that the yield of ...photodimerization products strongly depends on the structure and electronic properties of the material, primarily the electron affinity (acceptor strength) of the modified fullerene core. This finding being inconsistent with the conventional 2+2cycloaddition mechanism and pointed to an alternative pathway. This proposed pathway involves photoinduced charge separation followed by back charge transfer events leading to the efficient generation of triplet excitons, which are responsible for the formation of dimerized species. The light‐induced charge separation pathway was confirmed by electron spin resonance spectroscopy and was supported by theoretical calculations. The revealed mechanism allows one to control the photochemical behavior of the fullerene derivatives via rational structural engineering: some of the compounds were shown to be fully resistant to photodimerization, which makes them promising candidates in the development of stable organic photovoltaics. Furthermore, this approach could be used to suppress back charge transfer in donor‐acceptor blends and hinder the formation of triplet excitons which represents one a major energy loss channel in the current generation of organic solar cells.
A systematic study of a series of differently functionalized fullerene derivatives reveals that its light‐induced dimerization involves charge separation between the organic addend and carbon cage coupled with a back charge transfer (BCT) yielding reactive triplet states. This pathway appears to be general and provides a new tool to control the photostability organic semiconductors used as materials in solar cells.
•EthoStudio and 3-D sensor were applied for automated tracking of minpig behavior.•3-D sensor can trace white, black and agouti minipigs in the open field test.•Agouti minipigs explored arena more ...than white or black animals.•3-D imaging system can be used to study behavior of farm-bred animals.
The minipig is a promising model in neurobiology and psychopharmacology. However, automated tracking of minipig behavior is still unresolved problem.
The study was carried out on white, agouti and black (or spotted) minipiglets (n=108) bred in the Institute of Cytology and Genetics. New method of automated tracking of minipig behavior is based on Microsoft Kinect 3-D image sensor and the 3-D image reconstruction with EthoStudio software. The algorithms of distance run and time in the center evaluation were adapted for 3-D image data and new algorithm of vertical activity quantification was developed.
The 3-D imaging system successfully detects white, black, spotted and agouti pigs in the open field test (OFT). No effect of sex or color on horizontal (distance run), vertical activities and time in the center was shown. Agouti pigs explored the arena more intensive than white or black animals, respectively. The OFT behavioral traits were compared with the fear reaction to experimenter. Time in the center of the OFT was positively correlated with fear reaction rank (ρ=0.21, p<0.05). Black pigs were significantly more fearful compared with white or agouti animals.
The 3-D imaging system has three advantages over existing automated tracking systems: it avoids perspective distortion, distinguishes animals any color from any background and automatically evaluates vertical activity.
The 3-D imaging system can be successfully applied for automated measurement of minipig behavior in neurobiological and psychopharmacological experiments.
A new algorithm for long-term continuous computer recording and analysis of motor activity of a group of zebrafish in the home tank has been developed. The movements of a group of
Danio rerio
during ...the entire light period and for several days are recorded at a frequency of 1 frame/sec in the form of short (15 min) files. Then these files are analyzed by the unique DanioStudo software, which, using a threshold algorithm and appropriate masks, calculates for each frame the sum of pixels associated with fish (the sum of fish silhouettes), and for two consecutive frames, the sum of altered pixels (the sum of altered fish silhouettes). The following indexes are calculated: the rate of sum of silhouettes alteration as the ratio of the sum of altered silhouettes to the sum of silhouettes (1) and the time spent in the selected area of the home tank as the ratio of the sum of silhouettes in this area to the sum of silhouettes in the entire tank (2). The mean rate of silhouette alteration correlates to the length of the path travelled by the fish and, therefore, serves as a correct measure of the motor activity of a group of fish. Using these algorithms, completely new data were obtained: it was shown that the motor activity of fish remains constant throughout the entire light period, but depends on the size of the home tank. The proposed approach, together with the DanioStudio software, can be effective in studying the dynamics of changes in the behavior of fish under long-term exposure to short daylight, drugs and toxic substances.
The mechanisms of resistance to antidepressant drugs is a key and still unresolved problem of psychopharmacology. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) play a key role in the ...therapeutic effect of many antidepressants. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in 5-HT synthesis in the brain. We used zebrafish (
) as a promising model organism in order to elucidate the effect of TPH2 deficiency caused by p-chlorophenylalanine (pCPA) on the alterations in behavior and expression of 5-HT-related (
,
,
,
,
) and BDNF-related (
,
,
,
) genes in the brain after prolonged treatment with two antidepressants, inhibitors of 5-HT reuptake (fluoxetine) and oxidation (pargyline). In one experiment, zebrafish were treated for 72 h with 0.2 mg/L fluoxetine, 2 mg/L pCPA, or the drugs combination. In another experiment, zebrafish were treated for 72 h with 0.5 mg/L pargyline, 2 mg/L pCPA, or the drugs combination. Behavior was studied in the novel tank diving test, mRNA levels were assayed by qPCR, 5-HT and its metabolite concentrations were measured by HPLC. The effects of interaction between pCPA and the drugs on zebrafish behavior were observed: pCPA attenuated "surface dwelling" induced by the drugs. Fluoxetine decreased mRNA levels of
and
genes, while pargyline decreased mRNA levels of
and
genes. Pargyline reduced
,
and
genes mRNA concentration only in the zebrafish treated with pCPA. The results show that the disruption of the TPH2 function can cause a refractory to antidepressant treatment.
PDF
