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121.
The C-terminal fragment of the ribosomal P protein complexed to trichosanthin reveals the interaction between the ribosome-inactivating protein and the ribosome
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Priscilla Hiu-Mei Too Meiji Kit-Wan Ma Amanda Nga-Sze Mak Yuen-Ting Wong Christine Kit-Ching Tung Guang Zhu Shannon Wing-Ngor Au Kam-Bo Wong Pang-Chui Shaw 《Nucleic acids research》2009,37(2):602-610
Ribosome-inactivating proteins (RIPs) inhibit protein synthesis by enzymatically depurinating a specific adenine residue at the sarcin-ricin loop of the 28S rRNA, which thereby prevents the binding of elongation factors to the GTPase activation centre of the ribosome. Here, we present the 2.2 Å crystal structure of trichosanthin (TCS) complexed to the peptide SDDDMGFGLFD, which corresponds to the conserved C-terminal elongation factor binding domain of the ribosomal P protein. The N-terminal region of this peptide interacts with Lys173, Arg174 and Lys177 in TCS, while the C-terminal region is inserted into a hydrophobic pocket. The interaction with the P protein contributes to the ribosome-inactivating activity of TCS. This 11-mer C-terminal P peptide can be docked with selected important plant and bacterial RIPs, indicating that a similar interaction may also occur with other RIPs. 相似文献
122.
Jianfei Chao Haitao Li Ka-Wing Cheng Man-Shan Yu Raymond Chuen-Chung Chang Mingfu Wang 《The Journal of nutritional biochemistry》2010,21(6):482-489
Resveratrol (3,4′,5-trans-trihydroxystilbene) is a phytoalexin with emerging lines of evidence supporting its beneficial effects on cardiovascular systems and inhibition of carcinogenesis. It has also been reported that certain methylated resveratrol derivatives are more effective than resveratrol in the prevention/treatment of cancer. However, little is known about the impact of resveratrol and its derivatives on the development of Parkinson's disease. In this study, we compared the neuroprotective effects of resveratrol with four methylated (fully or partially) resveratrol derivatives against parkinsonian mimetic 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells. Release of lactate dehydrogenase and activity of caspase-3 triggered by 6-OHDA were significantly reduced by resveratrol and one of the methylated derivatives, pinostilbene (3,4′-dihydroxy-5-methoxystilbene), in a dose-dependent manner. In addition, pinostilbene exerted a potent neuroprotective effect with a wider effective concentration range than resveratrol. By using high-performance liquid chromatography, we found that uptake of pinostilbene into SH-SY5Y cells was significantly higher than that of resveratrol. Enhanced bioavailability may thus be a major factor contributing to the neuroprotective activity of pinostilbene. Moreover, Western blot analysis demonstrated that pinostilbene markedly attenuated the phosphorylation of JNK and c-Jun triggered by 6-OHDA. Besides, mammalian target of rapamycin kinase may be an intracellular target accounting for the neuroprotective effects of pinostilbene. Our findings demonstrate the potential of methylated stilbenes in neuroprotection and provide important information for further research in this field. 相似文献
123.
Sai Wang Seto Tsz Yan Lam Penelope Mei Yu Or Wayne Yuk Wai Lee Alice Lai Shan Au Christina Chui Wa Poon Rachel Wai Sum Li Shun Wan Chan John Hok Keung Yeung George Pak Heng Leung Simon Ming Yuen Lee Sai Ming Ngai Yiu Wa Kwan 《The Journal of nutritional biochemistry》2010,21(9):872-880
Folic acid supplementation provides beneficial effects on endothelial functions in patients with hyperhomocysteinemia. However, its effects on vascular functions under diabetic conditions are largely unknown. Therefore, the effect(s) of folic acid (5.7 and 71 μg/kg/day for 4 weeks) on aortic relaxation was investigated using obese/diabetic (+db/+db) mice and lean littermate (+db/+m) mice. Acetylcholine-induced relaxation in +db/+db mice was less than that observed in +db/+m mice. The reduced relaxation in +db/+db mice was restored by consumption of 71 μg/kg folic acid. Acetylcholine-induced relaxation (with and without folic acid treatment) was sensitive to NG-nitro-l-arginine methyl ester, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, geldanamycin and triciribine. In addition, acetylcholine-induced relaxation was attenuated by resistin. The plasma level of resistin in +db/+db mice was sevenfold higher than that measured in +db/+m mice, and the elevated plasma level of resistin in +db/+db mice was reduced by 25% after treatment with 71 μg/kg folic acid. Folic acid slightly increased the ratio of reduced glutathione to oxidized glutathione in +db/+db mice. Moreover, folic acid caused a reduction in PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression, an increase in the phosphorylation of endothelial nitric oxide synthase (eNOSSer1177) and AktSer473, and an enhanced interaction of heat shock protein 90 (HSP90) with eNOS in both strains, with greater magnitude observed in +db/+db mice. In conclusion, folic acid consumption improved blunted acetylcholine-induced relaxation in +db/+db mice. The mechanism may be, at least partly, attributed to enhancement of PI3K/HSP90/eNOS/Akt cascade, reduction in plasma resistin level, down-regulation of PTEN and slight modification of oxidative state. 相似文献
124.
Zong-Ping Zheng Jinyu Ma Ka-Wing Cheng Jianfei Chao Qin Zhu Raymond Chuen-Chung Chang Ming Zhao Zhi-Xiu Lin Mingfu Wang 《Phytochemistry》2010,71(17-18):2046-2051
Two sulfur-containing compounds, (S)-2-amino-5-((R)-1-carboxy-2-((E)-3-(4-hydroxy-3-methoxyphenyl)allylthio)ethyl-amino)-5-oxopentanoic acid (1) and (S)-2-amino-5-((R)-1-(carboxymethylamino)-3-((E)-3-(4-hydroxyphenyl)allylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid (2), and one 1H-pyrrole-2-carboxylic acid derivative, 6-(3-(1H-pyrrole-2-carbonyloxy)-2-hydroxypropoxy)-3,4,5-trihydroxy-tetrahydro-2H-pyran-2-carboxylic acid (3), together with eighteen known phenolic compounds, were isolated from the fruits of pineapple. Their structures were elucidated by a combination of spectroscopic analyses. Some of these compounds showed inhibitory activities against tyrosinase. The half maximal inhibitory concentration values of compounds 1, 4, 5, 6, 7 are lower than 1 mM. These compounds may contribute to the well-known anti-browning effect of pineapple juice and be potential skin whitening agents in cosmetic applications. 相似文献
125.
Mitchell L. Cordova Lance W. Bernard Kira K. Au Timothy J. Demchak Marcus B. Stone JoEllen M. Sefton 《Journal of electromyography and kinesiology》2010,20(2):348-353
Cryotherapy and ankle bracing are often used in conjunction as a treatment for ankle injury. No studies have evaluated the combined effect of these treatments on reflex responses during inversion perturbation. This study examined the combined influence of ankle bracing and joint cooling on peroneus longus (PL) muscle response during ankle inversion. A 2 × 2 RM factorial design guided this study; the independent variables were: ankle brace condition (lace-up brace, control), and treatment (ice, control), and the dependent variables studied were PL stretch reflex latency (ms), and PL stretch reflex amplitude (% of max). Twenty-four healthy participants completed 5 trials of a sudden inversion perturbation to the ankle/foot complex under each ankle brace and cryotherapy treatment condition. No two-way interaction was observed between ankle brace and treatment conditions on PL latency (P = 0.283) and amplitude (P = 0.884). The ankle brace condition did not differ from control on PL latency and amplitude. Cooling the ankle joint did not alter PL latency or amplitude compared to the no-ice treatment. Ankle bracing combined with joint cooling does not have a deleterious effect on dynamic ankle joint stabilization during an inversion perturbation in normal subjects. 相似文献
126.
Soumitra Rajagopal Yuxin Ji Kun Xu Yuhuan Li Kathleen Wicks Jiewei Liu Ka-Wing Wong Ira M. Herman Ralph R. Isberg Rachel J. Buchsbaum 《The Journal of biological chemistry》2010,285(23):18060-18071
The Rac exchange factor Tiam1 is involved in diverse cell functions and signaling pathways through multiple protein interactions, raising the question of how signaling and functional specificity are achieved. We have shown that Tiam1 interactions with different scaffold proteins activate different Rac-dependent pathways by recruiting specific Rac effector proteins, and reasoned that there must be regulatory mechanisms governing each interaction. Fibroblasts express at least two Tiam1-interacting proteins, insulin receptor substrate protein 53 kDa (IRSp53) and spinophilin. We used fluorescent resonance energy transfer (FRET) to measure localized Rac activation associated with IRSp53 and spinophilin complexes in individual fibroblasts to test this hypothesis. Pervanadate or platelet-derived growth factor induced localized Rac activation dependent on Tiam1 and IRSp53. Forskolin or epinephrine induced localized Rac activation dependent on Tiam1 and spinophilin. In spinophilin-deficient cells, Tiam1 co-localized with IRSp53 in response to pervanadate or platelet-derived growth factor. In IRSp53-deficient cells, Tiam1 co-localized with spinophilin in response to forskolin or epinephrine. Total cellular levels of activated Rac were affected only in cells with exogenous Tiam1, and were primarily increased in the membrane fraction. Downstream effects of Rac activation were also stimulus and scaffold-specific. Cell ruffling, spreading, and cell adhesion were dependent on IRSp53, but not spinophilin. Epinephrine decreased IRSp53-dependent adhesion and increased cell migration in a Rac and spinophilin-dependent fashion. These results support the idea that Tiam1 interactions with different scaffold proteins couple distinct upstream signals to localized Rac activation and specific downstream pathways, and suggest that manipulating Tiam1-scaffold interactions can modulate Rac-dependent cellular behaviors. 相似文献
127.
Karen M. Kassel Da Ryung Au Matthew J. Higgins Maria Hines Lee M. Graves 《The Journal of biological chemistry》2010,285(44):33727-33736
Cytidine triphosphate synthetase (CTPS) is the rate-limiting enzyme in de novo CTP synthesis and is required for the formation of RNA, DNA, and phospholipids. This study determined the kinetic properties of the individual human CTPS isozymes (hCTPS1 and hCTPS2) and regulation through substrate concentration, oligomerization, and phosphorylation. Kinetic analysis demonstrated that both hCTPS1 and hCTPS2 were maximally active at physiological concentrations of ATP, GTP, and glutamine, whereas the Km and IC50 values for the substrate UTP and the product CTP, respectively, were close to their physiological concentrations, indicating that the intracellular concentrations of UTP and CTP may precisely regulate hCTPS activity. Low serum treatment increased hCTPS2 phosphorylation, and five probable phosphorylation sites were identified in the hCTPS2 C-terminal domain. Metabolic labeling of hCTPS2 with [32P]H3PO4 demonstrated that Ser568 and Ser571 were two major phosphorylation sites, and additional studies demonstrated that Ser568 was phosphorylated by casein kinase 1 both in vitro and in vivo. Interestingly, mutation of Ser568 (S568A) but not Ser571 significantly increased hCTPS2 activity, demonstrating that Ser568 is a major inhibitory phosphorylation site. The S568A mutation had a greater effect on the glutamine than ammonia-dependent activity, indicating that phosphorylation of this site may influence the glutaminase domain of hCTPS2. Deletion of the C-terminal regulatory domain of hCTPS1 also greatly increased the Vmax of this enzyme. In summary, this is the first study to characterize the kinetic properties of hCTPS1 and hCTPS2 and to identify Ser568 as a major site of CTPS2 regulation by phosphorylation. 相似文献
128.
129.
Jurga Sakalauskaitė Aušra Brazaitytė Akvilė Urbonavičiūtė Giedrė Samuolienė Gintarė Šabajevienė Sandra Sakalauskienė Pavelas Duchovskis 《Central European Journal of Biology》2010,5(5):674-681
Effects of short-term ozone (O3) fumigation on radish (Raphanus sativus L.) plants were examined in growth chambers under controlled environment conditions. Plants were exposed to 0 μg/m3 (reference), 80 μg/m3, 160 μg/m3 and 240 μg/m3 O3 concentrations for 7 h per day for five days. Day/night temperature was 21°C/14°C and photoperiod 16 h. Chlorophyll content
was evaluated spectrophotometrically. Chromatographic analysis of saccharides was also undertaken. The results showed that
elevated O3 inhibited the growth of radish rhizocarps, net assimilation rate and biomass accumulation. O3 induced leaf desiccation, necrosis and premature senescence, but a typical reaction of plants to O3 stress was the rapid regeneration of new leaves. O3 inhibited accumulation of carotenoids more than chlorophylls. The higher photosynthetic pigment content in newly generated
radish leaves may be regarded as an adaptation of the photosynthetic system to O3. Leaf saccharide metabolism and incorporation depended on O3 concentration. Rapid regeneration of new leaves and increased content of photosynthetic pigments is the typical reaction
of radish plants to O3 stress. 相似文献
130.