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1.
Irine Yunhafita Malya Jing Wu Etsuko Harada Masaaki Toda Corina N. D’Alessandro-Gabazza Taro Yasuma 《Bioscience, biotechnology, and biochemistry》2020,84(7):1332-1338
ABSTRACT A novel compound, (R)-4-ethoxy-2-hydroxy-4-oxobutanoic acid (1), and six known compounds (2–7) were isolated from the fruiting bodies of the wild edible mushroom Leucopaxillus giganteus. The planar structure of 1 was determined by the interpretation of spectroscopic data analysis. The absolute configuration of 1 was determined by comparing specific rotation of the synthetic compounds. In the plant regulatory assay, the isolated compounds (1–7) and the chemically prepared compounds (8–10) were evaluated their biological activity against the lettuce (Lactuca sativa) growth. Compounds 1 and 3–10 showed the significant regulatory activity of lettuce growth. 1 showed the strongest inhibition activity among the all the compounds tested. In the lung cancer assay, all the compounds were assessed the mRNA expression of Axl and immune checkpoints (PD-L1, PD-L2) in the human A549 alveolar epithelial cell line by RT-PCR. Compounds 1–10 showed significant inhibition activity against Axl and/or immune checkpoint. 相似文献
2.
J. Monaselidze G. Majagaladze Sh. Barbakadze D. Khachidze M. Gorgoshidze Y. Kalandadze 《Journal of biomolecular structure & dynamics》2013,31(4):419-424
Abstract Thermodynamic parameters of melting process (δHm, Tm, δTm) of calf thymus DNA, poly(dA)poly(dT) and poly(d(A-C))·poly(d(G-T)) were determined in the presence of various concentrations of TOEPyP(4) and its Zn complex. The investigated porphyrins caused serious stabilization of calf thymus DNA and poly poly(dA)poly(dT), but not poly(d(A-C))poly(d(G-T)). It was shown that TOEpyp(4) revealed GC specificity, it increased Tm of satellite fraction by 24°C, but ZnTOEpyp(4), on the contrary, predominately bound with AT-rich sites and increased DNA main stage Tm by 18°C, and Tm of poly(dA)poly(dT) increased by 40 °C, in comparison with the same polymers without porphyrin. ZnTOEpyp(4) binds with DNA and poly(dA)poly(dT) in two modes—strong and weak ones. In the range of r from 0.005 to 0.08 both modes were fulfilled, and in the range of r from 0.165 to 0.25 only one mode—strong binding—took place. The weak binding is characterized with shifting of Tm by some grades, and for the strong binding Tm shifts by ~ 30–40°C. Invariability of ΔHm of DNA and poly(dA)poly(dT), and sharp increase of Tm in the range of r from 0.08 to 0.25 for thymus DNA and 0.01–0.2 for poly(dA)poly(dT) we interpret as entropic character of these complexes melting. It was suggested that this entropic character of melting is connected with forcing out of H2O molecules from AT sites by ZnTOEpyp(4) and with formation of outside stacking at the sites of binding. Four-fold decrease of calf thymus DNA melting range width ΔTm caused by increase of added ZnTO- Epyp(4) concentration is explained by rapprochement of AT and GC pairs thermal stability, and it is in agreement with a well-known dependence, according to which ΔT~TGC-TAT for DNA obtained from higher organisms (L. V. Berestetskaya, M. D. Frank-Kamenetskii, and Yu. S. Lazurkin. Biopolymers 13, 193–205 (1974)). Poly (d(A-C))poly(d(G-T)) in the presence of ZnTOEpyp(4) gives only one mode of weak binding. The conclusion is that binding of ZnTOEpyp(4) with DNA depends on its nucleotide sequence. 相似文献
3.
E. Zhuravliova T. Barbakadze N. Jojua E. Zaalishvili L. Shanshiashvili N. Natsvlishvili I. Kalandadze N. Narmania I. Chogovadze D. Mikeladze 《Cellular and molecular neurobiology》2012,32(8):1311-1321
Hypothyroidism in humans provokes various neuropsychiatric disorders, movement, and cognitive abnormalities that may greatly depend on the mitochondrial energy metabolism. Brain cells contain at least two major populations of mitochondria that include the non-synaptic mitochondria, which originate from neuronal and glial cell bodies (CM), and the synaptic (SM) mitochondria, which primarily originate from the nerve terminals. Several parameters of oxidative stress and other parameters in SM and CM fractions of hippocampus of adult rats were compared among euthyroid (control), hypothyroid (methimazol-treated), and thyroxine (T4)-treated hypothyroid states. nNOS translocation to CM was observed with concomitant increase of mtNOS??s activity in hypothyroid rats. In parallel, oxidation of cytochrome c oxidase and production of peroxides with substrates of complex I (glutamate?+?malate) were enhanced in CM, whereas the activity of aconitase and mitochondrial membrane potential (????m) were decreased. Furthermore, the elevation of mitochondrial hexokinase activity in CM was also found. No differences in these parameters between control and hypothyroid animals were observed in SM. However, in contrast to CM, hypothyroidism increases the level of pro-apoptotic K-Ras and Bad in SM. Our results suggest that hypothyroidism induces moderate and reversible oxidative/nitrosative stress in hippocampal CM, leading to the compensatory elevation of hexokinase activity and aerobic glycolysis. Such adaptive activation in glycolytic metabolism does not occur in SM, suggesting that synaptic mitochondria differ in their sensitivity to the energetic disturbance in hypothyroid conditions. 相似文献
4.
Giorgi Babuadze Jorge Alvar Daniel Argaw Harry P. de Koning Merab Iosava Merab Kekelidze Nikoloz Tsertsvadze David Tsereteli Giorgi Chakhunashvili Tamar Mamatsashvili Nino Beria Irine Kalandadze Mikhail Ejov Paata Imnadze 《PLoS neglected tropical diseases》2014,8(3)
This study investigated the transmission and prevalence of Leishmania parasite infection of humans in two foci of Visceral Leishmaniasis (VL) in Georgia, the well known focus in Tbilisi in the East, and in Kutaisi, a new focus in the West of the country. The seroprevalence of canine leishmaniasis was investigated in order to understand the zoonotic transmission. Blood samples of 1575 dogs (stray and pet) and 77 wild canids were tested for VL by Kalazar Detect rK39 rapid diagnostic tests. Three districts were investigated in Tbilisi and one in Kutaisi. The highest proportions of seropositive pet dogs were present in District #2 (28.1%, 82/292) and District #1 (26.9%, 24/89) in Tbilisi, compared to 17.3% (26/150) of pet dogs in Kutaisi. The percentage of seropositive stray dogs was also twice as high in Tbilisi (16.1%, n = 670) than in Kutaisi (8%, n = 50); only 2/58 wild animals screened were seropositive (2. 6%). A total of 873 Phlebotomine sand flies were collected, with 5 different species identified in Tbilisi and 3 species in Kutaisi; 2.3% of the females were positive for Leishmania parasites. The Leishmanin Skin Test (LST) was performed on 981 human subjects in VL foci in urban areas in Tbilisi and Kutaisi. A particularly high prevalence of LST positives was observed in Tbilisi District #1 (22.2%, 37.5% and 19.5% for ages 5–9, 15–24 and 25–59, respectively); lower prevalence was observed in Kutaisi (0%, 3.2% and 5.2%, respectively; P<0.05). This study shows that Tbilisi is an active focus for leishmaniasis and that the infection prevalence is very high in dogs and in humans. Although exposure is as yet not as high in Kutaisi, this is a new VL focus. The overall situation in the country is alarming and new control measures are urgently needed. 相似文献
5.
Michael Karpusas Irine Axarli Lykourgos Chiniadis Athanasios Papakyriakou Kostas Bethanis Katholiki Scopelitou Yannis D. Clonis Nikolaos E. Labrou 《PloS one》2013,8(2)
Glutathione transferases (GSTs) are enzymes that contribute to cellular detoxification by catalysing the nucleophilic attack of glutathione (GSH) on the electrophilic centre of a number of xenobiotic compounds, including several chemotherapeutic drugs. In the present work we investigated the interaction of the chemotherapeutic drug chlorambucil (CBL) with human GSTA1-1 (hGSTA1-1) using kinetic analysis, protein crystallography and molecular dynamics. In the presence of GSH, CBL behaves as an efficient substrate for hGSTA1-1. The rate-limiting step of the catalytic reaction between CBL and GSH is viscosity-dependent and kinetic data suggest that product release is rate-limiting. The crystal structure of the hGSTA1-1/CBL-GSH complex was solved at 2.1 Å resolution by molecular replacement. CBL is bound at the H-site attached to the thiol group of GSH, is partially ordered and exposed to the solvent, making specific interactions with the enzyme. Molecular dynamics simulations based on the crystal structure indicated high mobility of the CBL moiety and stabilization of the C-terminal helix due to the presence of the adduct. In the absence of GSH, CBL is shown to be an alkylating irreversible inhibitor for hGSTA1-1. Inactivation of the enzyme by CBL followed a biphasic pseudo-first-order saturation kinetics with approximately 1 mol of CBL per mol of dimeric enzyme being incorporated. Structural analysis suggested that the modifying residue is Cys112 which is located at the entrance of the H-site. The results are indicative of a structural communication between the subunits on the basis of mutually exclusive modification of Cys112, indicating that the two enzyme active sites are presumably coordinated. 相似文献
6.
Nina Gehde Corinna Hinrichs Irine Montilla Stefan Charpian Klaus Lingelbach Jude M. Przyborski 《Molecular microbiology》2009,71(3):613-628
Plasmodium falciparum traffics a large number of proteins to its host cell, the mature human erythrocyte. How exactly these proteins gain access to the red blood cell is poorly understood. Here we have investigated the effect of protein folding on the transport of model substrate proteins to the host cell. We find that proteins must pass into the erythrocyte cytoplasm in an unfolded state. Our data strongly support the presence of a protein-conducing channel in the parasitophorous vacoular membrane, and additionally imply an important role for molecular chaperones in keeping parasite proteins in a 'translocation competent' state prior to membrane passage. 相似文献
7.
Characterization of DNA pattern in the site of permanent attachment to the nuclear matrix located in the vicinity of replication origin 总被引:2,自引:0,他引:2
A G Kalandadze S A Bushara Y S Vassetzky S V Razin 《Biochemical and biophysical research communications》1990,168(1):9-15
The permanent sites of DNA attachment to the nuclear matrix in the domain of chicken alpha-globin genes originally found in erythrocyte nuclei have also been shown to exist in sperm and cultured fibroblast cells. A primary structure of a 1.7 kb fragment located in 5'-upstream region of chicken alpha-globin gene domain and containing both replication origin and permanent nuclear matrix attachment site has been determined. It was found to possess homologies with papovaviral replication origins and contain short internal repeats and GC-rich motifs. 相似文献
8.
Cecilia Bonnet Jan Rusz Marika Megrelishvili Tomá? Sieger Olga Matou?ková Michael Okujava Hana Bro?ová Tomá? Nikolai Jaromír Hanu?ka Mariam Kapianidze Nina Mikeladze Nazi Botchorishvili Irine Khatiashvili Marina Janelidze Tereza Serranová Ond?ej Fiala Jan Roth Jonas Bergquist Robert Jech Sophie Rivaud-Péchoux Bertrand Gaymard Ev?en R??i?ka 《PloS one》2014,9(8)
Patients with ephedrone parkinsonism (EP) show a complex, rapidly progressive, irreversible, and levodopa non-responsive parkinsonian and dystonic syndrome due to manganese intoxication. Eye movements may help to differentiate parkinsonian syndromes providing insights into which brain networks are affected in the underlying disease, but they have never been systematically studied in EP. Horizontal and vertical eye movements were recorded in 28 EP and compared to 21 Parkinson''s disease (PD) patients, and 27 age- and gender-matched healthy subjects using standardized oculomotor tasks with infrared videooculography. EP patients showed slow and hypometric horizontal saccades, an increased occurrence of square wave jerks, long latencies of vertical antisaccades, a high error rate in the horizontal antisaccade task, and made more errors than controls when pro- and antisaccades were mixed. Based on oculomotor performance, a direct differentiation between EP and PD was possible only by the velocity of horizontal saccades. All remaining metrics were similar between both patient groups. EP patients present extensive oculomotor disturbances probably due to manganese-induced damage to the basal ganglia, reflecting their role in oculomotor system. 相似文献
9.
One focus of our research is to further our understanding of the physico-chemical properties of non-canonical nucleic acid structures. In this work, DNA hairpins are used to mimic a common motif present in RNA, i.e. a stem-loop motif with a bulge or internal loop in their stem. Specifically, we used a combination of temperature-dependent UV spectroscopy, differential scanning (DSC), and pressure perturbation (PPC) calorimetric techniques to determine complete thermodynamic profiles for the helix–coil transitions of two sets of hairpins with 5′–3′ sequences: d(GCGCT n GTAACT5GTTACGCGC) and d(GCGCT n GTAACT5GTTACT n GCGC). “T n ” is a variable loop of thymines, n?=?1, 3 or 5; and “T5” is an end-loop of five thymines. Unfolding curves show monophasic transitions with TMs independent of strand concentration, confirming their intramolecular formation. DSC thermodynamic profiles indicate that the favorable folding of each hairpin results from the typical compensation of favorable enthalpy and unfavorable entropy contributions, while the DSC curves as a function of salt concentration yielded an uptake of cations and negative heat capacity effects. PPC melting curves yielded positive folding volumes ranging 12–31?cm3/mol, corresponding to releases of water molecules; in contrast, an uptake of water (ranging from 32 to 63?mol of H2O/mol) is observed from osmotic stress experiments using ethylene glycol as the osmolyte. Overall, the increase in the size of the variable bulge or internal-loop yielded lower TMs and slightly more favorable enthalpies, corresponding to less favorable free energy contributions of ~0.7?kcal/mol per thymine residue. The volume measurements will be correlated with the unfolding entropies and discussed in terms of the type of water that is hydrating these stem-loop motifs structures. 相似文献
10.
Monaselidze J Majagaladze G Barbakadze Sh Khachidze D Gorgoshidze M Kalandadze Y Haroutiunian S Dalyan Y Vardanyan V 《Journal of biomolecular structure & dynamics》2008,25(4):419-424
Thermodynamic parameters of melting process (DeltaHm, Tm, DeltaTm) of calf thymus DNA, poly(dA)poly(dT) and poly(d(A-C)).poly(d(G-T)) were determined in the presence of various concentrations of TOEPyP(4) and its Zn complex. The investigated porphyrins caused serious stabilization of calf thymus DNA and poly poly(dA)poly(dT), but not poly(d(A-C))poly(d(G-T)). It was shown that TOEpyp(4) revealed GC specificity, it increased Tm of satellite fraction by 24 degrees C, but ZnTOEpyp(4), on the contrary, predominantly bound with AT-rich sites and increased DNA main stage Tm by 18 degrees C, and Tm of poly(dA)poly(dT) increased by 40 degrees C, in comparison with the same polymers without porphyrin. ZnTOEpyp(4) binds with DNA and poly(dA)poly(dT) in two modes--strong and weak ones. In the range of r from 0.005 to 0.08 both modes were fulfilled, and in the range of r from 0.165 to 0.25 only one mode--strong binding--took place. The weak binding is characterized with shifting of Tm by some grades, and for the strong binding Tm shifts by approximately 30-40 degrees C. Invariability of DeltaHm of DNA and poly(dA)poly(dT), and sharp increase of Tm in the range of r from 0.08 to 0.25 for thymus DNA and 0.01-0.2 for poly(dA)poly(dT) we interpret as entropic character of these complexes melting. It was suggested that this entropic character of melting is connected with forcing out of H2O molecules from AT sites by ZnTOEpyp(4) and with formation of outside stacking at the sites of binding. Four-fold decrease of calf thymus DNA melting range width DeltaTm caused by increase of added ZnTOEpyp(4) concentration is explained by rapprochement of AT and GC pairs thermal stability, and it is in agreement with a well-known dependence, according to which DeltaT approximately TGC-TAT for DNA obtained from higher organisms (L. V. Berestetskaya, M. D. Frank-Kamenetskii, and Yu. S. Lazurkin. Biopolymers 13, 193-205 (1974)). Poly (d(A-C))poly(d(G-T)) in the presence of ZnTOEpyp(4) gives only one mode of weak binding. The conclusion is that binding of ZnTOEpyp(4) with DNA depends on its nucleotide sequence. 相似文献