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901.
902.
Involvement of the protein kinase pathway in melanin synthesis by chick retinal pigment epithelial cells 总被引:2,自引:0,他引:2
Protein kinases are involved in a variety of cellular functions and cell proliferation in eyes. We have explored the involvement of protein kinase C (PKC) in cell proliferation and melanin synthesis by chick retinal pigment epithelial (RPE) cells in vitro. This was achieved by incubation of confluent RPE cells with known inhibitors of protein kinase, H-7, W-7, H-8, and staurosporine. Chick RPE cells were cultured in the presence or absence of the protein kinase inhibitors for a 10-day period. Effects of the inhibitors on cell proliferation and melanin synthesis, as an indication of cell differentiation, were assessed by counting the number of surviving cells and by measuring the melanin content in the cells, respectively. H-7, W-7, and staurosporine inhibited cell proliferation and increased melanin synthesis in a concentration-dependent manner during culture; however, H-8 did not produce these cellular effects. These findings indicate that PKC and calcium/calmodulin-dependent kinase pathways are involved in the proliferation and differentiation of chick RPE cells. 相似文献
903.
Inhibitors of the carrier-mediated influx of auxin in suspension-cultured tobacco cells 总被引:6,自引:0,他引:6
Active auxin transport in plant cells is catalyzed by two carriers working in opposite directions at the plasma membrane,
the influx and efflux carriers. A role for the efflux carrier in polar auxin transport (PAT) in plants has been shown from
studies using phytotropins. Phytotropins have been invaluable in demonstrating that PAT is essential to ensure polarized and
coordinated growth and to provide plants with the capacity to respond to environmental stimuli. However, the function of the
influx carrier at the whole-plant level is unknown. Our work aims to identify new auxin-transport inhibitors which could be
employed to investigate its function. Thirty-five aryl and aryloxyalkylcarboxylic acids were assayed for their ability to
perturb the accumulation of 2,4-dichlorophenoxyacetic acid (2,4-D) and naphthalene-1-acetic acid (1-NAA) in suspension-cultured
tobacco (Nicotiana tabacum L.) cells. As 2,4-D and 1-NAA are preferentially transported by the influx and efflux carriers, respectively, accumulation
experiments utilizing synthetic auxins provide independant information on the activities of both carriers. The majority (60%)
of compounds half-inhibited the carrier-mediated influx of [14C]2,4-D at concentrations of less than 10 μM. Most failed to interfere with [3H]NAA efflux, at least in the short term. Even though they increasingly perturbed auxin efflux when given a prolonged treatment,
several compounds were much better at discriminating between influx and efflux carrier activities than naphthalene-2-acetic
acid which is commonly employed to investigate influx-carrier properties. Structure-activity relationships and factors influencing
ligand specificity with regard to auxin carriers are discussed.
Received: 28 June 1999 / Accepted: 28 August 1999 相似文献
904.
Parul Gupta Kamal Dhawan Sarla P Malhotra Randhir Singh 《Acta Physiologiae Plantarum》2000,22(4):433-438
A trypsin inhibitor from seeds of faba bean (Vicia faba L.) was purified to near homogeneity as judged by native-PAGE with about 11 % recovery using ammonium sulphate fractionation,
ion-exchange chromatography on DEAE-cellulose and gel filtration through Sephadex G-100. The inhibitor had a molecular weight
of 18 kD as determined by SDS-PAGE and Sephadex G-100. The inhibitor inhibited trypsin and chymotrypsin to the extent of 48
and 12 %, respectively. The inhibtion was of non-competitive type with dissociation constant for the enzyme inhibitor complex
in the region of 0.07 mg·ml−1. The inhibtor was stable between pH 4 and 5. It completely lost its activity when heated at 125 °C for 1 h or at 100 °C for
2 h. The inhibitor also lost its activity on exposure to 2-mercaptoethanol. Based on these properties, it could be concluded
that Vicia faba trypsin inhibitor belongs to Bowman-Birk type of inhibitors, as it has molecular weight lower than generally observed for
Kunitz type inhibitors. 相似文献
905.
We studied temporal and spatial expression patterns of the potato proteinase inhibitor II (PI-II) promoter, using transgenic
tobacco (Nkotiana tabacum L cv. Xanthi) plants that carried a fusion between the PI-II promoter and the chloramphenicol acetyltransferase (cat) gene. Pl-ll promoter activity was low when plants were young, but increased as plants grew. In 8-week-old plants, old leaves
showed higher activity than young leaves. At flowering stage (ca. 15 weeks), the overall promoter activity was reduced to
a lower level except in the petals. Compared with stems or petioles at the flowering stage, the roots and floral organs showed
minimal activity for the Pl-ll promoter. We used several environmental stimuli to examine the induction of the Pl-ll promoter
in different organs. Promoter induction was effected by wounding or methyl jasmonate in stems, petioles, sepals, and leaves.
The induction was highest in leaves, as was sucrose-enhanced wound induction. These results suggest that the Pl-ll gene is
temporally and spatially regulated. We also established a transient assay system in tobacco BY2 suspension cells to elucidate
the upstream regulatory region of the Pl-ll promoter. A field strength of 0.75 kV/cm and 400 μF capacitance were optimal electroporation
conditions for our transient assay. 相似文献
906.
Miura T Fukami TA Hasegawa K Ono N Suda A Shindo H Yoon DO Kim SJ Na YJ Aoki Y Shimma N Tsukuda T Shiratori Y 《Bioorganic & medicinal chemistry letters》2011,21(19):5778-5783
Heat shock protein 90 (Hsp90) is a molecular chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models. 相似文献
907.
Advanced glycation end-products (AGEs) are one of the major factors of hyperglycemia related complications for diabetic patients. We studied the formation of AGEs in type I collagen after Fe2+-catalyzed non-enzymatic glycosylation in vitro. Type I collagen isolated from rat tail tendon was incubated with glucose and increasing concentrations of iron ions Fe2+. After 4 weeks incubation, cytotoxity of AGEs was indicated by the cytotoxity assay of primary human umbilical vein endothelial cells and primary human monocytes cultured with glycosylated collagen AGEs. Fourier transform infrared spectroscopy analysis revealed that structural changes of functional groups in glycosylated collagen are accelerated by the catalyst Fe2+. Using two-dimensional Fourier-transform infrared correlation spectroscopy analyses, for the first time, we demonstrated that the order of structural changes of these functional groups is -CH- > Amide I > Amide II > Amide III > ν(CO) the carboxylic group of Asn, Gln or polyproline amino acid residue in the course of AGE-collagen formation. Knowing the positions of these functional groups in collagen, this order of changes indicates that during glycation of collagen, the structure of the main chain residues in collagen changed first, and then the side chain changed gradually, which may lead to more carboxylic groups exposed to glucose for further formation of AGE-collagen irreversibly. The findings presented may support the design of new therapeutic strategies to prevent or slow down the Fe2+-catalyzed glycosylation of collagen and other matrix proteins. 相似文献
908.
Wang Y Wang SY Zhang XH Zhao M Hou CM Xu YJ Du ZY Yu XD 《Biochemical and biophysical research communications》2007,356(4):998-1003
Some pan-histone-deacetylase (HDAC) inhibitors have recently been reported to exert their anti-leukemia effect by inhibiting the activity of class IIB HDAC6, which is the deacetylase of Hsp90 and α-tubulin, thereby leading to hyperacetylation of Hsp90, disruption of its chaperone function and apoptosis. In this study, we compared the effect of a class I HDAC inhibitor FK228 with the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on the Hsp90 chaperone function of K562 cells. We demonstrated that, although having a weaker inhibitory effect on HDAC6, FK228 mediated a similar disruption of Hsp90 chaperone function compared to SAHA. Unlike SAHA, FK228 did not mediate hyperacetylation of Hsp90, instead the acetylation of Hsp70 was increased and Bcr-Abl was increasingly associated with Hsp70 rather than Hsp90, forming an unstable complex that promotes Bcr-Abl degradation. These results indicated that FK228 may disrupt the function of Hsp90 indirectly through acetylation of Hsp70 and inhibition of its function. 相似文献
909.
Tie Y Kovalevsky AY Boross P Wang YF Ghosh AK Tozser J Harrison RW Weber IT 《Proteins》2007,68(1):232-242
Due to the limited distance data available from the experiments, the structures determined by NMR Spectroscopy may not always be as accurate as desired. Further refinement of the structures is often required and sometimes critical. With the increase of high quality protein structures determined and deposited in PDB Data Bank, commonly shared protein conformational properties can be extracted based on the statistical distributions of the properties in the structural database and used to improve the outcomes of the NMR-determined structures. Here we examine the distributions of protein interatomic distances in known protein structures. We show that based on these distributions, a set of mean-force potentials can be defined for proteins and employed to refine the NMR-determined structures. We report the test results on 70 NMR-determined structures and compare the potential energy, the Ramachandran plot, and the ensemble RMSD of the structures refined with and without using the derived mean-force potentials. 相似文献
910.
The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) is induced by glucocorticoids (GCs), but it was not previously known if MIF regulates cellular sensitivity to GC. Here we show in GC and LPS-treated peritoneal macrophages derived from MIF-/- and wt mice that the absence of endogenous MIF is associated with increased sensitivity to GC of TNF release. This is associated with increased expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), concomitant decreased phosphorylation of p38 MAPK, but no effect of MIF on nuclear factor kappaB (NF-kappaB). These results demonstrate that MIF regulates GC sensitivity by phosphorylation of p38, and provides a cellular mechanism for this observation, indicating that MKP-1 is a central target of this regulation. 相似文献