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61.
62.
Lee KO Lee JR Yoo JY Jang HH Moon JC Jung BG Chi YH Park SK Lee SS Lim CO Yun DJ Cho MJ Lee SY 《Biochemical and biophysical research communications》2002,296(5):1152-1156
Glutaredoxin (Grx) is a 12-kDa thioltransferase that reduces disulfide bonds of other proteins and maintains the redox potential of cells. In addition to its oxidoreductase activity, we report here that a rice Grx (OsGrx) can also function as a GSH-dependent peroxidase. Because of this antioxidant activity, OsGrx protects glutamine synthetase from oxidative damage. Individually replacing the conserved Cys residues in OsGrx with Ser shows that Cys(23), but not Cys(26), is essential for the thioltransferase and GSH-dependent peroxidase activities. Kinetic characterization of OsGrx reveals that the maximal catalytic efficiency (V(max)/K(m)) is obtained with cumene hydroperoxide rather than H(2)O(2) or t-butyl hydroperoxide. 相似文献
63.
Inhibitor of apoptosis proteins (IAPs) are a conserved class of proteins that control apoptosis in both vertebrates and invertebrates. They exert their anti-apoptotic function through inhibition of caspases, the principal executioners of apoptotic cell death. Recent advances in vertebrates and Drosophila have demonstrated that IAPs use ubiquitin conjugation to control the stability, and thus the activity, of select target proteins. The Drosophila IAP1 gene is an instructive example: it employs at least two distinct ubiquitin-dependent mechanisms of protein destruction. The apoptosis-inducing genes grim, reaper and hid modulate these mechanisms, and determine the outcome. 相似文献
64.
Mice with a defect in the xeroderma pigmentosum group A (XPA) gene have a complete deficiency in nucleotide excision repair (NER). As such, these mice mimic the human XP phenotype in that they have a >1000-fold higher risk of developing UV-induced skin cancer. Besides being UV-sensitive, XPA−/− mice also develop internal tumors when they are exposed to chemical carcinogens. To investigate the effect of a total NER deficiency on the induction of gene mutations and tumor development, we crossed XPA−/− mice with transgenic lacZ/pUR288 mutation-indicator mice. The mice were treated with various agents and chemicals like UV-B, benzo[a]pyrene and 2-aceto-amino-fluorene. Gene mutation induction in several tumor target- and non-target tissues was determined in both the bacterial lacZ reporter gene and in the endogenous Hprt gene. Furthermore, alterations in the p53- and ras genes were determined in UV-induced skin tumors of XPA−/− mice. In this work, we review these results and discuss the applicability and reliability of enhanced gene mutant frequencies as early indicators of tumorigenesis. 相似文献
65.
Induction of 72-kDa Inducible Heat Shock Protein (HSP72) in Cultured Rat Astrocytes After Energy Depletion 总被引:2,自引:1,他引:1
Naohiko Imuta Satoshi Ogawa ‡Yusuke Maeda †Keisuke Kuwabara †Osamu Hori Hirokazu Ueda Takehiko Yanagihara Masaya Tohyama 《Journal of neurochemistry》1998,70(2):550-557
Abstract: Protein synthesis is important in the readaptive processes for cultured astrocytes after hypoxia and subsequent reoxygenation. We have identified 72-kDa inducible heat shock protein (HSP72) as a major stress protein in reoxygenated astrocytes. To assess the mechanism for reoxygenation-mediated induction of HSP72, a reporter gene that consists of a human HSP promoter fused to the luciferase gene was transfected into cultured astrocytes. Analysis of cellular energy nucleotides showed an increase of the ADP/ATP ratio after reoxygenation, which synchronized with activation of the HSP promoter. Activation of the HSP promoter was also observed after an addition of iodoacetic acid to hypoxic astrocytes, which reached the maximum when the ADP/ATP ratio reached 50%, but further decline in the energy profile caused inactivation of this promoter. Inhibition of protein synthesis after reoxygenation resulted in temporary restoration of the energy profile and suppression of the DNA binding activity of the heat shock factor. Addition of quercetin greatly decreased the [3 H]leucine incorporation in the polysome fraction without any effect on the mature mRNA formation. These data suggest that the energy depletion in reoxygenation triggers induction of HSP72 after reoxygenation, which may act as a pivotal mediator in the stress response of reoxygenated astrocytes by facilitating protein synthesis. 相似文献
66.
R S Power H E David M H A Z Mutwakil K Fletcher C Daniells M A Nowell J L Dennis A Martinelli R Wiseman E Wharf D I de Pomerai 《Journal of biosciences》1998,23(4):513-526
This paper reviews the current status of nematodes with stress-inducible transgenes as biosensors responsive to a range of
external stressors, e.g., soil or water pollution, microwave radiation or immunological attack. TransgenicCaenorhabditis elegans carrying reporter genes under heat shock promoter control express reporter products only under stressful conditions. Although
relatively insensitive to single metal ions, these worms respond to complex mixtures present in metal-contaminated watercourses
and to laboratory mixtures containing similar constituents, but not to any of their components singly at comparable concentrations.
Responses to metal mixtures are enhanced by a non-ionic surfactant, Pluronic F-127. Metals taken up by food bacteria and insoluble
metal carbonates can also evoke stress responses, both in soil and aqueous media. However, high concentrations of added metals
are needed to induce clear-cut responses in soil, owing to metal sorption onto clays and organic matter. Transgenic worms
are also stressed by exposure to microwave radiation; pulsed signals generate responses that diminish markedly with distance
from the source. Finally, stress responses are inducible by anti-epicuticle antisera and complement, suggesting that immune
attack can also activite the heat shock system. The development of rapid microplate toxicity assays based on transgenic nematodes
is discussed. 相似文献
67.
68.
Cheng-Chung Wu Hong-Jin Wu Chia-Hui Wang Chia-Hua Lin Shu-Ching Hsu Yi-Rong Chen Michael Hsiao Scott C Schuyler Frank Leigh Lu Nianhan Ma Jean Lu 《Cell cycle (Georgetown, Tex.)》2015,14(8):1207-1217
Mouse embryonic stem cells (ES cells) can proliferate indefinitely. To identify potential signals involved in suppression of self-renewal, we previously screened a kinase/phosphatase expression library in ES cells, and observed that inhibition of Dual Leucine zipper-bearing Kinase (DLK) increased relative cell numbers. DLK protein was detected in both the pluripotent and differentiated states of mouse ES cells while DLK kinase activity increased upon differentiation. Overexpression of DLK in mouse ES cells displayed reductions in relative cell/colony numbers and Nanog expression, suggesting a suppressive role of DLK in self-renewal. By examining protein sequences of DLK, we identified 2 putative Akt phosphorylation sites at S584 and T659. Blocking PI3K/Akt signaling with LY-294002 enhanced DLK kinase activity dramatically. We found that Akt interacts with and phosphorylates DLK. Mutations of DLK amino acid residues at putative Akt phosphorylation sites (S584A, T659A, or S584A and T659A) diminished the level of DLK phosphorylation. While the mutated DLKs (S584A, T659A, or S584A and T659A) were expressed, a further reduction in cell/colony numbers and Nanog expression appeared in mouse ES cells. In addition, these mutant DLKs (S584A, T659A, or S584A and T659A) exhibited more robust kinase activity and cell death compared to wild type DLK or green fluorescence (GFP) controls. In summary, our results show that DLK functions to suppress self-renewal of mouse ES cells and is restrained by Akt phosphorylation. 相似文献
69.
70.
Promoter analysis typically employs a reporter gene fused to a test promoter combined with a second reporter fused to a control promoter that is used for normalization purposes. However, this approach is not valid when experimental conditions affect the control promoter. We have developed and validated a single secreted luciferase reporter (SSLR) assay for promoter analysis that avoids the use of a control reporter. The approach uses an early level of expression of a secreted luciferase linked to a test promoter as an internal normalization control for subsequent analysis of the same promoter. Comparison of the SSLR assay with the dual luciferase reporter (DLR) assay using HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and LDLR (low-density lipoprotein receptor) promoter constructs, which are down-regulated by 25-hydroxycholesterol, show that both assays yield similar results. Comparison of the response of the HMGCR promoter in SSLR transient assays compared very favorably with the response of the same promoter in the stable cell line. Overall, the SSLR assay proved to be a valid alternative to the DLR assay for certain applications and had significant advantages in that measurement of only one luciferase is required and monitoring can be continuous because cell lysis is not necessary. 相似文献