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991.
Cyclooxygenase-2 (COX-2) is reported to be one of the early-response gene products induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the relevance of COX-2 in TPA-induced cell transformation and the underlying mechanisms remains to be explored. Initially, we verified COX-2 induction after TPA treatment in mouse embryonic fibroblasts (MEF) and mouse epidermal cells Cl 41. More importantly, introduction of COX-2 small interfering RNA in MEFs or Cl 41 cells suppressed the cell transformation caused by TPA treatment. This inhibition could be reversed by overexpression of human full-length COX-2, indicating that COX-2 is at least one of the critical molecules involved in TPA-induced cell transformation. We further showed that TPA-promoted cell cycle progression was partially suppressed by COX-2 small interfering RNA, indicating that COX-2 also participated in TPA-associated cell cycle progression. Investigation of the upstream signaling pathways revealed that c-Jun-NH(2)-kinase 1 (JNK1), but not JNK2, played important roles in COX-2 induction, because knockout of JNK1 gene rather than JNK2 gene markedly impaired COX-2 induction. Furthermore, inhibition of c-Jun/activator protein 1 pathway or JNKs/c-Jun pathway by overexpression of dominant negative mutants of c-Jun, or MKK4 and MKK7 together, resulted in impairment of COX-2 induction, suggesting that JNK1/c-Jun/activator protein 1 pathway is involved in TPA-associated COX-2 induction. In contrast, IKK/p65 nuclear factor-kappaB pathway was not implicated because knockout of IKKalpha, IKKbeta, or p65 gene did not affect COX-2 induction although nuclear factor-kappaB was activated by TPA. In addition, the TPA-promoted cell cycle progression was found impaired in JNK1-deficient, but not in JNK2-deficient, MEFs. Our results show that JNK1-associated COX-2 induction is implicated in TPA-associated cell transformation and cell cycle progression. 相似文献
992.
993.
Pre-synaptic dopaminergic compensation after moderate nigrostriatal damage in non-human primates 总被引:2,自引:0,他引:2
Despite a dramatic loss of nigrostriatal dopaminergic neurons in Parkinson's disease, clinical symptoms only arise with 70–80% reduction of striatal dopamine. The mechanisms responsible for this functional compensation are currently under debate. Although initial studies showed an enhanced pre-synaptic dopaminergic function with nigrostriatal degeneration, more recent work suggests that functional compensation is not dopamine-mediated. To address this issue, we used cyclic voltammetry to directly measure endogenous dopamine release from striatal slices of control monkeys and animals with a moderate or severe MPTP-induced dopaminergic lesion. The moderately lesioned monkeys were asymptomatic, while the severely lesioned animals were parkinsonian. In monkeys with a moderate lesion, a 300% increase was obtained in endogenous striatal dopamine release. In contrast, in striatal slices from severely lesioned animals, a small % of evoked dopamine signals were similar in amplitude to control while the greater majority were undetectable. These findings suggest that pre-synaptic dopaminergic compensation develops in residual dopaminergic terminals with moderate lesioning, but that this response is lost with severe nigrostriatal damage. Such an interpretation is supported by the results of dopamine turnover studies. This enhanced pre-synaptic dopaminergic activity may be important in maintaining normal motor function during the initial stages of Parkinson's disease. 相似文献
994.
995.
Jones LL Colf LA Bankovich AJ Stone JD Gao YG Chan CM Huang RH Garcia KC Kranz DM 《Biochemistry》2008,47(47):12398-12408
To understand the mechanisms that govern T cell receptor (TCR)-peptide MHC (pMHC) binding and the role that different regions of the TCR play in affinity and antigen specificity, we have studied the TCR from T cell clone 2C. High-affinity mutants of the 2C TCR that bind QL9-L(d) as a strong agonist were generated previously by site-directed mutagenesis of complementarity determining regions (CDRs) 1beta, 2alpha, 3alpha, or 3beta. We performed isothermal titration calorimetry to assess whether they use similar thermodynamic mechanisms to achieve high affinity for QL9-L(d). Four of the five TCRs examined bound to QL9-L(d) in an enthalpically driven, entropically unfavorable manner. In contrast, the high-affinity CDR1beta mutant resembled the wild-type 2C TCR interaction, with favorable entropy. To assess fine specificity, we measured the binding and kinetics of these mutants for both QL9-L(d) and a single amino acid peptide variant of QL9, called QL9-Y5-L(d). While 2C and most of the mutants had equal or higher affinity for the Y5 variant than for QL9, mutant CDR1beta exhibited 8-fold lower affinity for Y5 compared to QL9. To examine possible structural correlates of the thermodynamic and fine specificity signatures of the TCRs, the structure of unliganded QL9-L(d) was solved and compared to structures of the 2C TCR/QL9-L(d) complex and three high-affinity TCR/QL9-L(d) complexes. Our findings show that the QL9-L(d) complex does not undergo major conformational changes upon binding. Thus, subtle changes in individual CDRs account for the diverse thermodynamic and kinetic binding mechanisms and for the different peptide fine specificities. 相似文献
996.
Guoqin Huang Xiuying Liu Longwang Liu Fang Ye Mingling Zhang Yanhong Shu 《Frontiers of Biology in China》2008,3(3):344-350
According to the principles and methods of ecology and system engineering, we set up an evaluation indicator system for multi-component
and multiple cropping systems, evaluated the comprehensive benefits of multi-component and multiple cropping systems using
grey relation clustering analysis and screened out the optimized model based on research done in the upland red soil in Jiangxi
Agricultural University from 1984 to 2004. The results show that the grey relation degree of “cabbage/potato/maize — sesame”
was the highest among 23 multi-component and multiple cropping systems and was clustered into the optimized system. This indicates
that “cabbage/potato/maize — sesame” can bring the best social, economic and ecological benefits, increase product yield and
farmers’ income and promote sustainable development of agricultural production. Therefore, it is suitable for promotion on
upland red soil. The grey relation degree of “canola/Chinese milk vetch/maize/mung bean/maize” was second, which is suitable
for implementation at the city outskirts. In conclusion, these two planting patterns are expected to play important roles
in the reconstruction of the planting structure and optimization of the planting patterns on upland red soil.
__________
Translated from Acta Ecologica Sinica, 2006, 26(8): 2532–2539 [译自: 生态学报] 相似文献
997.
We have previously shown that electroacupuncture (EA) produced antinociception through the release of endogenous opioid peptides
to activate opioid receptors during acute nociception. EA produced tolerance after its prolonged application. It has reported
that 100 Hz EA could reduce mechanical hyperalgesia in complete Freund’s adjuvant (CFA)-induced inflammatory nociception rats.
The present study aims to investigate the antinociceptive effect of EA and the development of EA tolerance in chronic inflammatory
nociception rats with CFA injection into the hind paw plantar. The results showed that the antinociceptive effect of 100 Hz
EA was significantly enhanced in CFA-induced inflammatory nociception rats. Naloxone at 20 mg/kg could significantly block
this antinociceptive effect. Chronic tolerance to EA was developed faster in CFA-induced inflammatory nociception rats than
in normal rats. Therefore, 100 Hz EA could enhance antinociceptive effects and accelerate tolerance development in CFA-induced
inflammatory nociception rats. The enhancement of EA antinociceptive effect in CFA-induced inflammatory nociception rats might
involve the endogenous opioid peptides such as dynorphin.
Special issue article in honor of Dr. Ji-Sheng Han. 相似文献
998.
Effects of lanthanum on rumen fermentation, urinary excretion of purine derivatives and digestibility in steers 总被引:3,自引:0,他引:3
Q. Liu C. Wang Y.X. Huang K.H. Dong W.Z. Yang H. Wang 《Animal Feed Science and Technology》2008,142(1-2):121-132
The objective of this study was to evaluate the effects of LaCl3 supplementation on rumen fermentation, urinary excretion of purine derivatives and feed digestibility in the total tract of steers. Eight ruminally cannulated Simmental steers (420 ± 20 kg) were used in a replicated 4 × 4 Latin square experiment. The treatments were control (without LaCl3); La-low; La-medium and La-high with 450, 900 and 1800 mg LaCl3 per steer per day, respectively. Diet consisted of 600 g/kg corn stover and 400 g/kg concentrate (dry matter [DM] basis). Dry matter intake (averaged 9 kg/day) was restricted to a maximum of 90% of ad libitum intake. Ruminal pH (range of 6.59–6.42) was quadratically (P<0.04) changed, whereas total volatile fatty acids (VFA) concentration (range of 74.16–88.61 mM) was linearly (P<0.01) and quadratically (P<0.01) increased with increasing La supplementation. Ratio of acetate to propionate decreased linearly (P<0.01) from 3.28 to 1.79 as La supplementation increased due to the increased in propionate production. In situ ruminal neutral detergent fibre (aNDF) degradation of corn stover was improved but the crude protein (CP) degradability of soybean meal was decreased with increasing La supplementation. Urinary excretion of purine derivatives was quadratically (P<0.01) changed with altering La supplementation (75.5, 81.0, 82.4 and 70.6 mmol/day for control, low-, medium- and high-LaCl3 supplementation, respectively). Similarly, digestibilities of organic matter, aNDF and CP in the total tract were also linearly and quadratically increased with increasing La supplementation. The present results indicate that supplementation of diet with LaCl3 improved rumen fermentation and feed digestion in beef cattle. It was suggested that the La stimulated the digestive microorganisms or enzymes in a dose-dependent manner. In the experimental conditions of this trial, the optimum La dose was about 900 mg LaCl3 per steer per day. 相似文献
999.
Huang RB Du QS Wang CH Chou KC 《Biochemical and biophysical research communications》2008,377(4):1243-1247
The long-sought three-dimensional structure of the M2 proton channel of influenza A virus was successfully determined recently by the high-resolution NMR [J.R. Schnell, J.J. Chou, Structure and mechanism of the M2 proton channel of influenza A virus, Nature 451 (2008) 591-595]. Such a milestone work has provided a solid structural basis for studying drug-resistance problems. However, the action mechanism revealed from the NMR structure is completely different from the traditional view and hence prone to be misinterpreted as “conflicting” with some previous biological functional studies. To clarify this kind of confusion, an in-depth analysis was performed for these functional studies, particularly for the mutations D44N, D44A and N44D on position 44, and the mutations on positions 27-38. The analyzed results have provided not only compelling evidences to further validate the NMR structure but also very useful clues for dealing with the drug-resistance problems and developing new effective drugs against H5N1 avian influenza virus, an impending threat to human beings. 相似文献
1000.
The Hedgehog (Hh) signal is transmitted by two receptor molecules, Patched (Ptc) and Smoothened (Smo). Ptc suppresses Smo activity, while Hh binds Ptc and alleviates the suppression, which results in activation of Hh targets. Smo is a seven-transmembrane protein with a long carboxyl terminal tail. Vertebrate Smo has been previously shown to be coupled to Gαi proteins, but the biological significance of the coupling in Hh signal transduction is not clear. Here we show that although inhibition of Gαi protein activity appears to significantly reduce Hh pathway activity in Ptc−/− mouse embryonic fibroblasts and the NIH3T3-based Shh-light cells, it fails to derepress Shh- or a Smo-agonist-induced inhibition of Gli3 protein processing, a known in vivo indicator of Hh signaling activity. The inhibition of Gαi protein activity also cannot block the Sonic Hedgehog (Shh)-dependent specification of neural progenitor cells in the neural tube. Consistent with these results, overexpression of a constitutively active Gαi protein, Gαi2QL, cannot ectopically specify the neural cell types in the spinal cord, whereas an active Smo, SmoM2, can. Thus, our results indicate that the Smo-induced Gαi activity plays an insignificant role in the regulation of Gli3 processing and Shh-regulated neural tube patterning. 相似文献