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61.
Induction of a hypertrophic growth status of coronary smooth muscle cells is associated with an overexpression of TGF-beta 总被引:4,自引:0,他引:4
Schmidt A Göpfert C Vlodavsky I Völker W Buddecke E 《European journal of cell biology》2002,81(3):138-144
Hypertrophy of vascular smooth muscle cells occurs during hypertension-induced remodelling of arteries and during development of arteriosclerosis and restenosis following angioplasty but the pathogenesis of the hypertrophic status is not yet fully understood. In a previous study we demonstrated that the synthetic non-sulfated, non-toxic heparin-mimicking compound RG-13577 is capable of inducing a cell cycle-arrested hypertrophic phenotype of coronary smooth muscle cells. In this study we clarify the mode of action of RG-13577 and demonstrate that the RG-13577-induced hypertrophy is associated with an increased expression of TGF-beta1 as indicated by an increase in TGF-beta1-specific protein and mRNA level. Furthermore we show that RG-13577-treated hypertrophic smooth muscle cells maintain full metabolic activity as indicated by a continuous de novo synthesis of protein and proteoglycans and that the RG-13577-induced growth arrest is caused not only by a higher expression of TGF-beta, but also by a reduced response of RG-treated cells to the mitogenic activity of bFGF, PDGF and EGF. The growth inhibitory activity of RG-13577 is reduced in the presence of neutralizing antibodies against TGF-beta. TGF-beta itself has anti-proliferative activity in serum-depleted medium. The RG-13577 effect is reversible since incubation of hypertrophic cells in RG-13577-free medium restores cell volume and [3H]thymidine incorporation to the values of untreated control cells within 4 days. We conclude, that the active metabolic status of RG-13577-treated cells in association with the overexpression of TGF-beta could promote repair processes of injured arteries after angioplasty without stimulating cell proliferation. 相似文献
62.
63.
Polyoma-infected 3T6 cells contain a number of proteins precipitable by serum from rats carrying polyoma-induced tumors. The virus codes for three species having apparent molecular weights of 90,000, 60,000 and 22,000 daltons, as determined by polyacrylamide gel electrophoresis (90K, 60K and 22k). The 90K and 22K species produced by a large plaque and a small plaque wild-type polyoma have similar mobilities, but the 60K species produced by the large plaque wild-type. In cells infected by each of seven polyoma tsA mutants, the 90K species is unstable at the nonpermissive temperature, while the 60K and 22K species are stable. In cells infected by a mutant carrying a deletion between roughly 98 and 3 map units in the early region of the viral genome, the 22K species is present, but the 90K and 60K species are absent. Tryptic peptide analysis of the isolated 90K, 60K and 22K species shows that the three species have common N terminal regions. The 60K and 22K species contain amino acid sequences not found in the 90K species , and the 60K species has several unique, methionine-containing peptides not found in either the 22K or 90K species. Two polyoma-transformed BHK cell lines do not have detectable amounts of the 90K protein. 相似文献
64.
T Hunter M A Hutchinson W Eckhart T Friedmann A Esty P LaPorte P Deininger 《Nucleic acids research》1979,7(8):2275-2288
The early region of the polyoma genome encodes three T antigens. We have analyzed the organization of the coding regions for the T antigens, using the nucleotide sequence of polyoma DNA and peptides derived from purified, radio-labeled T antigens, separated by two-dimensional electrophoresis and chromatography. We compared the peptides, predicted from the nucleotide sequence of the DNA, with those derived from the purified T antigens. We also compared chemically synthesized peptides, predicted from the DNA sequence, with observed peptides. The results show that the three polyoma T antigens are encoded in overlapping regions of the viral DNA, translated, in part, in two different reading frames. 相似文献
65.
Okamoto K Ocker M Neureiter D Dietze O Zopf S Hahn EG Herold C 《Journal of cellular and molecular medicine》2007,11(2):349-361
Gemcitabine has been shown to ameliorate disease related symptoms and to prolong overall survival in pancreatic cancer.Yet, resistance to Gemcitabine is commonly observed in this tumour entity and has been linked to increased expression of anti-apoptotic bcl-2. We therefore investigated if and to what extend silencing of bcl-2 by specific siRNAs (siBCL2) might enhance Gemcitabine effects in human pancreatic carcinoma cells. siBCL2 was transfected into the pancreatic cancer cell line YAP C alone and 72 hrs before co-incubation with different concentrations of Gemcitabine. Total protein and RNA were extracted for Western-blot analysis and quantitative polymerase chain reaction. Pancreatic cancer xenografts in male nude mice were treated intraperitoneally with siBCL2 alone, Gemcitabine and control siRNA or Gemcitabine and siBCL2 for 21 days. Combination of both methods lead to a synergistic induction of apoptosis at otherwise ineffective concentrations of Gemcitabine. Tumour growth suppression was also potentiated by the combined treatment with siBCL2 and Gemcitabine in vivo and lead to increased TUNEL positivity. In contrast, non-transformed human foreskin fibroblasts showed only minor responses to this treatment. Our results demonstrate that siRNA-mediated silencing of anti-apoptotic bcl-2 enhances chemotherapy sensitivity in human pancreatic cancer cells in vitro and might lead to improved therapy responses in advanced stages of this disease. 相似文献
66.
Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain 总被引:111,自引:0,他引:111
We introduced two mutations into the carboxy-terminal regulatory region of chicken pp60c-src. One, F527, replaces tyrosine 527 with phenylalanine. The other, Am517, produces a truncated pp60c-src protein lacking the 17 carboxy-terminal amino acids. Both mutant proteins were phosphorylated at tyrosine 416 in vivo. The specific activity of the Am517 mutant protein kinase was similar to that of wild-type pp60c-src whereas that of the F527 mutant was 5- to 10-fold higher. Both mutant c-src genes induced focus formation on NIH 3T3 cells, but the foci appeared at lower frequency, and were smaller than foci induced by polyoma middle tumor antigen (mT). The wild-type or F527 pp60c-src formed a complex with mT, whereas the Am517 pp60c-src did not. The results suggest that one, inability to phosphorylate tyrosine 527 increases pp60c-src protein kinase activity and transforming ability; two, transformation by mT involves other events besides lack of phosphorylation at tyrosine 527 of pp60c-src; three, activation of the pp60c-src protein kinase may not be required for transformation by the Am517 mutant; and four, the carboxyl terminus of pp60c-src appears to be required for association with mT. 相似文献
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68.
Hans Weidmann Dietmar Tartler Peter Stöckl Leo Binder Helmut Hönig 《Carbohydrate research》1973,29(1):135-140
Acylation of 2-amino-1,3,4,6-tetra-O-benzoyl-2-deoxy-α-D-glucopyranose yielded various 2-acylamido-1,3,4,6-tetra-O-benzoyl-2-deoxy-α-D-glucopyranoses, which on treatment with hydrogen bromide-acetic acid gave halogenoses, oxazolinium bromides or 2-bromo-oxazolidinium bromides depending on the N-acyl substituent. It was found that acetyl bromide-hydrogen bromide is a particularly suited reagent for such transformations. 相似文献
69.
Gerhard Burkl Helga Castorph Eckhart Schweizer 《Molecular & general genetics : MGG》1972,119(4):315-322
Summary Using two different experimental approaches—UV induced mitotic recombination and meiotic segregation—a fatty acid synthetase gene locus has been mapped on chromosome Fragment V of the Saccharomyces cerevisiae genetic map. This locus has been tentatively designated as fas1AB since it is a complex locus coding for at least two different fatty acid synthetase component enzymes, namely the -hydroxyacid dehydratase and the enoyl reductase. According to the meiotic segregation patterns obtained, fas1AB is 41.6 centimorgans from ura1 and 35.7 centimorgans from trp3. Furthermore, the same criteria of mitotic sectoring and meiotic segregation indicate that the second known fatty acid synthetase gene cluster in yeast is genetically unlinked to fas1AB or to any other of the known genetic loci on Fragment V. 相似文献
70.