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1.
V. N. Anisimov L. E. Bakeeva P. A. Egormin O. F. Filenko E. F. Isakova V. N. Manskikh V. M. Mikhelson A. A. Panteleeva E. G. Pasyukova D. I. Pilipenko T. S. Piskunova I. G. Popovich N. V. Roshchina O. Yu. Rybina V. B. Saprunova T. A. Samoylova A. V. Semenchenko M. V. Skulachev I. M. Spivak E. A. Tsybul’ko M. L. Tyndyk M. Yu. Vyssokikh M. N. Yurova M. A. Zabezhinsky V. P. Skulachev 《Biochemistry. Biokhimii?a》2008,73(12):1329-1342
Very low (nano- and subnanomolar) concentrations of 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SkQ1) were found to
prolong lifespan of a fungus (Podospora anserina), a crustacean (Ceriodaphnia affinis), an insect (Drosophila melanogaster), and a mammal (mouse). In the latter case, median lifespan is doubled if animals live in a non-sterile vivarium. The lifespan
increase is accompanied by rectangularization of the survival curves (an increase in survival is much larger at early than
at late ages) and disappearance of typical traits of senescence or retardation of their development. Data summarized here
and in the preceding papers of this series suggest that mitochondria-targeted antioxidant SkQ1 is competent in slowing down
execution of an aging program responsible for development of age-related senescence.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.
Published in Russian in Biokhimiya, 2008, Vol. 73, No. 12, pp. 1655–1670. 相似文献
2.
V. V. Neroev M. M. Archipova L. E. Bakeeva A. Zh. Fursova E. N. Grigorian A. Yu. Grishanova E. N. Iomdina Zh. N. Ivashchenko L. A. Katargina I. P. Khoroshilova-Maslova O. V. Kilina N. G. Kolosova E. P. Kopenkin S. S. Korshunov N. A. Kovaleva Yu. P. Novikova P. P. Philippov D. I. Pilipenko O. V. Robustova V. B. Saprunova I. I. Senin M. V. Skulachev L. F. Sotnikova N. A. Stefanova N. K. Tikhomirova I. V. Tsapenko A. I. Shchipanova R. A. Zinovkin V. P. Skulachev 《Biochemistry. Biokhimii?a》2008,73(12):1317-1328
Mitochondria-targeted cationic plastoquinone derivative SkQ1 (10-(6′-plastoquinonyl) decyltriphenylphosphonium) has been investigated
as a potential tool for treating a number of ROS-related ocular diseases. In OXYS rats suffering from a ROS-induced progeria,
very small amounts of SkQ1 (50 nmol/kg per day) added to food were found to prevent development of age_induced cataract and
retinopathies of the eye, lipid peroxidation and protein carbonylation in skeletal muscles, as well as a decrease in bone
mineralization. Instillation of drops of 250 nM SkQ1 reversed cataract and retinopathies in 3-12-month-old (but not in 24-month-old)
OXYS rats. In rabbits, experimental uveitis and glaucoma were induced by immunization with arrestin and injections of hydroxypropyl
methyl cellulose to the eye anterior sector, respectively. Uveitis was found to be prevented or reversed by instillation of
250 nM SkQ1 drops (four drops per day). Development of glaucoma was retarded by drops of 5 μM SkQ1 (one drop daily). SkQ1
was tested in veterinarian practice. A totally of 271 animals (dogs, cats, and horses) suffering from retinopathies, uveitis,
conjunctivitis, and cornea diseases were treated with drops of 250 nM SkQ1. In 242 cases, positive therapeutic effect was
obvious. Among animals suffering from retinopathies, 89 were blind. In 67 cases, vision returned after SkQ1 treatment. In
ex vivo studies of cultivated posterior retina sector, it was found that 20 nM SkQ1 strongly decreased macrophagal transformation
of the retinal pigmented epithelial cells, an effect which might explain some of the above SkQ1 activities. It is concluded
that low concentrations of SkQ1 are promising in treating retinopathies, cataract, uveitis, glaucoma, and some other ocular
diseases.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.
Published in Russian in Biokhimiya, 2008, Vol. 73, No. 12, pp. 1641–1654. 相似文献
3.
Y. N. Antonenko A. V. Avetisyan L. E. Bakeeva B. V. Chernyak V. A. Chertkov L. V. Domnina O. Yu. Ivanova D. S. Izyumov L. S. Khailova S. S. Klishin G. A. Korshunova K. G. Lyamzaev M. S. Muntyan O. K. Nepryakhina A. A. Pashkovskaya O. Yu. Pletjushkina A. V. Pustovidko V. A. Roginsky T. I. Rokitskaya E. K. Ruuge V. B. Saprunova I. I. Severina R. A. Simonyan I. V. Skulachev M. V. Skulachev N. V. Sumbatyan I. V. Sviryaeva V. N. Tashlitsky J. M. Vassiliev M. Yu. Vyssokikh L. S. Yaguzhinsky A. A. Zamyatnin Jr. V. P. Skulachev 《Biochemistry. Biokhimii?a》2008,73(12):1273-1287
Synthesis of cationic plastoquinone derivatives (SkQs) containing positively charged phosphonium or rhodamine moieties connected
to plastoquinone by decane or pentane linkers is described. It is shown that SkQs (i) easily penetrate through planar, mitochondrial,
and outer cell membranes, (ii) at low (nanomolar) concentrations, posses strong antioxidant activity in aqueous solution,
BLM, lipid micelles, liposomes, isolated mitochondria, and cells, (iii) at higher (micromolar) concentrations, show pronounced
prooxidant activity, the “window” between anti- and prooxidant concentrations being very much larger than for MitoQ, a cationic
ubiquinone derivative showing very much lower antioxidant activity and higher prooxidant activity, (iv) are reduced by the
respiratory chain to SkQH2, the rate of oxidation of SkQH2 being lower than the rate of SkQ reduction, and (v) prevent oxidation of mitochondrial cardiolipin by OH·. In HeLa cells and human fibroblasts, SkQs operate as powerful inhibitors of the ROS-induced apoptosis and necrosis. For
the two most active SkQs, namely SkQ1 and SkQR1, C
1/2 values for inhibition of the H2O2-induced apoptosis in fibroblasts appear to be as low as 1·10−11 and 8·10−13 M, respectively. SkQR1, a fluorescent representative of the SkQ family, specifically stains a single type of organelles in
the living cell, i.e. energized mitochondria. Such specificity is explained by the fact that it is the mitochondrial matrix
that is the only negatively-charged compartment inside the cell. Assuming that the Δψ values on the outer cell and inner mitochondrial
membranes are about 60 and 180 mV, respectively, and taking into account distribution coefficient of SkQ1 between lipid and
water (about 13,000: 1), the SkQ1 concentration in the inner leaflet of the inner mitochondrial membrane should be 1.3·108 times higher than in the extracellular space. This explains the very high efficiency of such compounds in experiments on
cell cultures. It is concluded that SkQs are rechargeable, mitochondria-targeted antioxidants of very high efficiency and
specificity. Therefore, they might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner
mitochondrial membrane in vivo.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.
Published in Russian in Biokhimiya, 2008, Vol. 73, No. 12, pp. 1589–1606.
This and the following four articles were written by the request of the Editorial Board of Biochemistry (Moscow). 相似文献
4.
L. E. Bakeeva I. V. Barskov M. V. Egorov N. K. Isaev V. I. Kapelko A. V. Kazachenko V. I. Kirpatovsky S. V. Kozlovsky V. L. Lakomkin S. B. Levina O. I. Pisarenko E. Y. Plotnikov V. B. Saprunova L. I. Serebryakova M. V. Skulachev E. V. Stelmashook I. M. Studneva O. V. Tskitishvili A. K. Vasilyeva I. V. Victorov D. B. Zorov V. P. Skulachev 《Biochemistry. Biokhimii?a》2008,73(12):1288-1299
Effects of 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SkQ1) and 10-(6′-plastoquinonyl) decylrhod-amine 19 (SkQR1) on
rat models of H2O2- and ischemia-induced heart arrhythmia, heart infarction, kidney ischemia, and stroke have been studied ex vivo and in vivo. In all the models listed, SkQ1 and/or SkQR1 showed pronounced protective effect. Supplementation of food with extremely
low SkQ1 amount (down to 0.02 nmol SkQ1/kg per day for 3 weeks) was found to abolish the steady heart arrhythmia caused by
perfusion of isolated rat heart with H2O2 or by ischemia/reperfusion. Higher SkQ1 (125–250 nmol/kg per day for 2–3 weeks) was found to decrease the heart infarction
region induced by an in vivo ischemia/reperfusion and lowered the blood levels of lactate dehydrogenase and creatine kinase increasing as a result of
ischemia/reperfusion. In single-kidney rats, ischemia/reperfusion of the kidney was shown to kill the majority of the animals
in 2–4 days, whereas one injection of SkQ1 or SkQR1 (1 μmol/kg a day before ischemia) saved lives of almost all treated rats.
Effect of SkQR1 was accompanied by decrease in ROS (reactive oxygen species) level in kidney cells as well as by partial or
complete normalization of blood creatinine and of some other kidney-controlled parameters. On the other hand, this amount
of SkQ1 (a SkQ derivative of lower membrane-penetrating ability than SkQR1) saved the life but failed to normalize ROS and
creatinine levels. Such an effect indicates that death under conditions of partial kidney dysfunction is mediated by an organ
of vital importance other than kidney, the organ in question being an SkQ1 target. In a model of compression brain ischemia/reperfusion,
a single intraperitoneal injection of SkQR1 to a rat (1 μmol/kg a day before operation) effectively decreased the damaged
brain area. SkQ1 was ineffective, most probably due to lower permeability of the blood-brain barrier to this compound.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.
Published in Russian in Biokhimiya, 2008, Vol. 73, No. 12, pp. 1607–1621. 相似文献
5.
Hendrik Verschueren 《Cell biology and toxicology》1985,1(3):145-157
In vitro directional migration of 10 T1/2 fibroblasts is partially inhibited by TPA but not by its non promoting analogues. Other tumor promoters, e.g., phenobarbital, saccharin, and benzoylperoxide had no measurable effect when added in concentrations known to affect in vitro two-step transformation or intercellular communication. Inhibitors of in vitro transformation do not affect migration, except for dexamethasone, which inhibited it. Hence, there is no evidence for a general correlation between tumor promoting potential and inhibition of in vitro directional migration.Abbreviations DDT
1,1,1-trichloro-2,2-bis(p-cholorophenyl) ethane
- DEXA
dexamethasone
- DMSO
dimethylsulfoxide
- RA
retinylacetate
- SD
standard deviation
- SOD
superoxide dismutase
- TPA
12-0-tetradecanoylphorbol-13-acetate; 4-0-Me-TPA, 4-0-methyl-TPA 相似文献
6.
目的观察GPR30受体激动剂G1对高糖诱导的EA.hy926内皮细胞内质网应激(endoplasmic reticulum stress,ERS)的影响。方法选用EA.hy926内皮细胞为研究对象,分为3组:正常对照组(Con,17.51mmol/L葡萄糖)、高糖组(HG,33.3mmol/L葡萄糖)、高糖+G1组(HG+G1,HG+1umol/L G1),利用流式细胞术检测3组细胞凋亡率,Western blot法检测ERS相关分子Bip、IRE1、PERK及凋亡分子Bax、Bcl-2的表达变化,RT-PCR法检测Bip和CHOP的mRNA表达变化。结果 HG组与Con组比较,细胞凋亡率明显升高(P0.01),Bip、IRE1、PERK及凋亡分子Bax表达上调(P0.01,P0.05或P0.001),Bcl-2的表达下调(P0.01),Bip mRNA、CHOP mRNA表达上调(P0.001及P0.01);HG+G1组与HG组比较,细胞凋亡率明显降低(P0.05),Bip、IRE1、PERK及凋亡分子Bax表达下调(P0.05或P0.01),Bcl-2的表达上调(P0.05),Bip mRNA、CHOP mRNA表达下调(P0.001及P0.01)。结论 GPR30受体激动剂G1可抑制EA.hy926内皮细胞内质网应激。 相似文献
7.
Francesco Caruso Claudio Pettinari Fabio Marchetti Miriam Rossi Cristian Opazo Sarvesh Kumar Sakshi Balwani Balaram Ghosh 《Bioorganic & medicinal chemistry》2009,17(17):6166-6172
Recent reports show that the natural β-diketone curcumin displays important biological properties regarding the intercellular adhesion molecule-1 (ICAM-1), which plays a critical role in the immune responses and inflammation. In this study the ICAM-1 inhibitory activity of β-diketone compounds, which are curcumin models lacking aromatic peripheral hydroxyl and methoxy groups, along with some metal derivatives is investigated. β-Diketones are systematically more active than metal complexes and the best obtained inhibition is 75% for both groups. The best inhibitors are 4-benzoyl-3-methyl-1-phenyl-pyrazol-5-one (HQPh) among the ligands, and sodium benzoylacetonato among metal derivatives. These results appear in line with the reported antitumor activity of related species. Since 4-acyl-5-pyrazolones posses four tautomeric forms, those corresponding to HQPh were investigated using density functional theory. Docking of all HQPh tautomers on ICAM-1 protein was performed suggesting one keto-enol form favored to act in biological environment. 相似文献
8.
Hai-Sheng Liu Yu-Huan Gao Li-Hong Liu Qing-Wen Shi 《Bioscience, biotechnology, and biochemistry》2016,80(10):1883-1886
The inhibitory effect of 13 taxanes isolated from the Chinese yew (Taxus chinensis var. mairei) on the proliferation of human cervical cancer HeLa cells were examined using an MTT assay. Four compounds having a hydrophobic cinnamate side chain showed antiproliferative activity, which may be due to increased cell permeability. 相似文献
9.
Jing Liu Zhenzhou Jiang Jingwei Xiao Yun Zhang Sensen Lin Weigang Duan Jincheng Yao Chunhui Liu Xin Huang Tao Wang Zhongliang Liang Rongrong Wang Shuang Zhang Luyong Zhang 《Phytomedicine》2009,16(11):1006-1013
The aim of the study was to discover possible differential cytotoxicity of triptolide towards estrogen-sensitive MCF-7 versus estrogen-insensitive MDA-MB-231 human breast cancer cells. Considering that MCF-7 cells express functional Estrogen receptor α (ERα) and wild-type p53, whereas MDA-MB-231 cells which are ERα-negative express mutant p53, the anti-proliferation effect of triptolide on MCF-7 and MDA-MB-231 cells were examined, the apoptotic effect and cell cycle arrest caused by triptolide were investigated, ERα and p53 expression were also observed in this paper. The results showed that the anti-proliferation effects were induced by triptolide in both cell lines. But the value of IC50 in MCF-7 cells for its anti-proliferation effect was about one tenth of that in MDA-MB-231 cells, which indicated that the effect is more potent in MCF-7 cells. Condensed chromatin or fragmented nuclei could be found in MCF-7 cells treated with only 40 nM triptolide but in MDA-MB-231 cells they couldn’t be observed until the concentration reached to 400 nM. Triptolide induced significant S cell cycle arrest along with the presence of sub-G0/G1 peak in MDA-MB-231 cells, whereas there was only slightly S cell cycle arrest on cell cycle distribution in MCF-7 cells. The role of p53 in two breast cancer cells was examined, the results showed that the mutant p53 in MDA-MB-231 cells was suppressed and the wild-type p53 in MCF-7 was increased. Moreover, triptolide could down regulate the expression of ERα in MCF-7 cells. The results showed that triptolide is much more sensitive to ERα-positive MCF-7 cells than to ERα-negative MDA-MB-231 cells, and the sensitivity is significantly associated with the ERα and p53 status. 相似文献
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After exposing a line of rat liver epithelial cells to a single dose of the carcinogen N-acetoxy-2-acetylaminofluorene (N-acetoxy-AAF), a dose-dependent decrease in [3H]uridine incorporation into total cellular RNA was found. Approx. 50% inhibition occurred with 0.5 μg/ml of the compound. The kinetics of the response, the effects of actinomycin D, and the fractionation of the newly synthesized RNA by polyacrylamide gel electrophoresis indicated preferential inhibition of the synthesis of 45S ribosomal RNA precursor and a relative sparing of the synthesis of heterogeneous nuclear RNA. 相似文献
12.
Haploid loss of bax leads to accelerated mammary tumor development in C3(1)/SV40-TAg transgenic mice: reduction in protective apoptotic response at the preneoplastic stage. 下载免费PDF全文
M A Shibata M L Liu M C Knudson E Shibata K Yoshidome T Bandey S J Korsmeyer J E Green 《The EMBO journal》1999,18(10):2692-2701
The dramatic increase in apoptosis observed during the development of preneoplastic mammary lesions is associated with a significant elevation in Bax expression in C3(1)/SV40 large T antigen (TAg) transgenic mice. The significance of Bax expression during tumor progression in vivo was studied by generating double-transgenic mice carrying the C3(1)/TAg transgene and mutant alleles for bax. C3(1)/TAg transgenic mice carrying mutant bax alleles exhibited accelerated rates of tumor growth, increased tumor numbers, larger tumor mass and decreased survival rates compared with mice carrying wild-type bax. Accelerated tumorigenesis associated with the bax+/- genotype did not require the loss of function of the second bax allele. Thus, haploid insufficiency of bax is enough to accelerate tumor progression, suggesting that the protective effect of Bax is dose-dependent. While levels of apoptosis in the preneoplastic lesions, but not carcinomas, were reduced in bax+/- or bax-/- mice compared with bax+/+ mice, rates of cellular proliferation in mammary lesions were similar among all bax genotypes. These data demonstrate that bax is a critical suppressor of mammary tumor progression at the stage of preneoplastic mammary lesion development through the upregulation of apoptosis, but that this protective effect is lost during the transition from preneoplasia to invasive carcinoma. 相似文献
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特种五谷虫脂肪酸的体外抗肿瘤、抗HIV-1整合酶活性及组成分析 总被引:5,自引:0,他引:5
为研究特种五谷虫(大头金蝇Chrysomya megacephala蝇蛆的俗称)脂肪酸的体外抗肿瘤、抗HIV-1整合酶活性,并确定其组分构成,通过溶剂萃取和油脂酶解获得2种脂肪酸FA1和FA2,采用MTT法/SRB法测定其体外抗人白血病细胞HL-60/人肺癌细胞A-549活性,以及采用Biotin-ELISA法检测其对HIV-1整合酶的抑制作用;并由GC-MS分析确定其脂肪酸组成。结果表明:FA1和FA2对人白血病细胞/人肺癌细胞均有显著的抑制活性,其IC50值在35~65 μg/mL;对HIV-1整合酶同样具有强烈的抑制活性,IC50值分别为86.7 μg/mL和98.5 μg/mL。GC-MS分析表明,FA1和FA2化学组成相似,均含有15%~16%的多不饱和脂肪酸(PUFA),其中有2个组分为ω-6 PUFA。提示特定培养的五谷虫,其脂肪酸成分具有显著的体外抗肿瘤、抗HIV-1整合酶活性,其中含有的PUFA,尤其ω-6 PUFA,可能是主要活性组分;FA2在来源上和FA1存有相关性。 相似文献
15.
Wang Y Zhang M Tan Y Xiang Y Liu H Qu F Qin L Qin X 《Cell biology international》2007,31(12):1495-1500
Airway re-modelling in asthma usually results in an irreversible weakness of pulmonary ventilation, however, its initiating or controlling mechanism remains unclear. In this study, we hypothesize that signal communication between airway epithelial cells and sub-mucosal fibroblast cells may play an important role in the maintenance of structure homeostasis in a physiologic condition and in initiation of airway remodelling in a stressed condition. To test the hypothesis, a co-cultured system of human bronchial epithelial cells (BEC) and human lung fibroblasts (HLF) were designed to observe the effects of BEC, in the normal state or in a BRS-3 activated state, on the proliferation and collagen synthesis of HLF. The results showed that the proliferation activities of both BEC and HLF inhibited each other under the normal state. BRS-3-activated BEC can transform the reciprocal inhibition into promoting effects. The secretion of TGF-beta1 increased and the synthesis of PGE2 decreased from BRS-3-activated BEC, which were correlated with the proliferation and collagen synthesis of HLF. The proliferation activities of HLF were weakened by co-culture with TGF-beta1 antisense oligonucleotides (ASO) treated BEC. It was concluded that, in the normal state, BEC inhibits the activities of fibroblasts through release of PGE2 to maintain the airway homeostasis; however when stressed, for example by BRS-3 activation, BEC promote the activities of fibroblasts mediated by TGF-beta1, thereby facilitating the airway re-modelling. 相似文献
16.
Susana Johann Daniele L. Silva Cleide V. B. Martins Carlos L. Zani Moacir G. Pizzolatti Maria A. Resende 《World journal of microbiology & biotechnology》2008,24(11):2459-2464
Plants are known to produce a plethora of secondary metabolites which are recognized as a useful source of new drugs or drug
leads. Extracts and fractions of Schinus terebinthifolius Raddi (Anacardiaceae), Piper regnellii C.D.C. (Piperaceae), Rumex acetosa L. (Polygonaceae), and Punica granatum L. (Punicaceae) were assessed for their antifungal activity against eight clinical isolates of C. albicans. They were also evaluated for their effect on the adhesion of these C. albicans isolates to buccal epithelial cells (BECs). The ethyl acetate fraction from the leaves of S. terebinthifolius showed promising activity, inhibiting the growth of three C. albicans isolates at 7.8 μg ml−1 and significantly inhibiting their adhesion to BEC at 15 μg ml−1
. In addition, this fraction did not show cytotoxic activity against murine macrophages. The results show the potential of
the plant extracts studied as a source of new antifungal compounds. Further studies are necessary for isolation and characterization
of the active compounds of these plants. 相似文献
17.
BACKGROUND: CG beta is expressed not only in placenta, but also in a wide range of tumors. To study DNA vaccine based on xenogeneic CG beta for cancer immuno-therapy, we investigated whether rhesus monkey CG beta (rmCG beta) DNA vaccine could induce protective T-cell responses and humoral responses in mouse. METHODS: We constructed a plasmid containing the rmCG beta coding sequence. Two cloned syngeneic SP2/0 myeloma cell lines that stably express muCG beta l (SP2/0-muCG beta l) and HN (SP2/0-HN) protein were established. Inoculation of these cell lines was made into mice that had been immunized with DNA vaccine. Specific IgG and IgG type were measured by ELISA and the cytokine expression was detected with RT-PCR. To measure the lymphocyte metabolic activity, the MTS assay was used. RESULTS: After injection of SP2/0-muCG beta l into mice that had been immunized with DNA vaccine, a significant increase in the IgG2a specific to the antigen (p < 0.05) and a decrease in the specific IgG1 (p < 0.05) were measured. The expression of T(H)1 but not T(H)2 cytokines, including IFN-gamma and IL-2, were detected in the splenocytes. However, injection of tumor cells expressing irrelevant or mock molecules into immunized mice could not induce these changes. The survival rate of vaccine-immunized mice injected with SP2/0-muCG beta l was as high as 58.3% after 55 days. CONCLUSIONS: The rmCG beta DNA vaccine has proved to be a potential strategy for protection against tumors with homologous molecules. The muCG beta l produced by tumors is able to elicit an immunity switch from T(H)2 to T(H)1 in vaccinated mice. 相似文献
18.