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1.
A Pajunen A Crozat O A J?nne R Ihalainen P H Laitinen B Stanley R Madhubala A E Pegg 《The Journal of biological chemistry》1988,263(32):17040-17049
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Oligodeoxynucleotides 18 nucleotides in length having sequences complementary to regions spanning the initiation codon regions of ornithine decarboyxlase or S-adenosylmethionine decarboxylase mRNAs were tested for their ability to inhibit translation of these mRNAs. In reticulocyte lysates, a strong and dose dependent reduction of ornithine decarboyxlase synthesis in response to mRNA from D-R L1210 cells was brought about by 5-AAAGCT GCTCATGGTTCT-3 which is complementary to the sequence from - 6 to + 12 of the mRNA sequence but there was no inhibition by 5-TGCAGCTTCCATCACCGT-3. Conversely, the latter oligodeoxynucleotide which is complementary to the sequence from – 6 to + 12 of the mRNA of S-adenosyl methionine decarboxylase was a strong inhibitor of the synthesis of this enzyme in response to rat prostate mRNA and the antisense sequence from ornithine decarboxylase had no effect. The translation of ornithine decarboxylase mRNA in a wheat germ system was inhibited by the antisense oligodeoxynucleotide at much lower concentration than those needed in the reticulocyte lysate suggesting that degradation of the hybrid by ribonuclease H may be an important factor in this inhibition. These results indicate that such oligonucleotides may be useful to regulate cellular polyamine levels and as probes to study control of mRNA translation.Abbreviations ODC
ornithine decarboxylase
- AdoMetDC
S-adenosylmethionine decarboxylase
- DFMO
difluoromethylornithine 相似文献
3.
Intratesticular injection of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha) caused stimulation of ornithine decarboxylase (ODC) activity in the testis of immature rats. PGE2 at a dose of 10 microgram per testis was maximally effective 2 hours after the injection. Dibutyryl cyclic AMP (cAMP) and 1 methyl, 3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor, also stimulated ODC activity. Simultaneous injection of PGE2 and FSH or LH caused additional stimulation of ODC activity. Similarly injection of PGE2 in addition to cAMP or MIX also caused increased stimulation of ODC. Indomethacin (IM, 60 microgram/testis) inhibited LH, FSH or cAMP induced ODC activity. However, IM at the same dose inhibited the synthesis of total proteins. These results suggest that PGE2 and PGF2 alpha stimulate the activity of ODC. The action of prostaglandins may be independent of the action of gonadotropic hormones. cAMP appears to mediate the action of prostaglandins in the testis of rat. 相似文献
4.
Leishmaniasis, a spectrum of diseases caused by various forms of Leishmania has become a major health problem all over the world. Vaccination against leishmaniasis has passed through many developmental stages beginning with the ancient practice of 'leishmanization'. Due to various problems and difficulties associated with traditional vaccines, the interest has been shifted to novel approaches of vaccination like DNA vaccination, vaccination with live vectors encoding leishmanial antigens and finally to designer vaccines. In an effort towards developing an anti-leishmanial vaccine, our laboratory has been working on various genes present in an amplified locus of Leishmania known as the 'LD1 locus'. Two genes, ORFF and BT1 (previously ORFG), are part of the multigenic LD1 locus on chromosome 35. BT1 encodes a biopterin transporter, while the function of ORFF gene product is unknown. Immunization of mice with recombinant ORFF (rORFF) and BT1 proteins, individually, or in combination, conferred partial protection against challenge with Leishmania donovani. We also tested the protective efficacy of ORFF DNA vaccine in BALB/c mice model and found that the level of protection was significantly higher than that of ORFF protein. Protection conferred by ORFF DNA vaccine correlated with significant levels of in vitro splenocyte proliferation and low levels of antigen-specific antibodies. There was a preferential production of IFN-gamma compared to IL-4, which indicated the induction of a protective Th1 response, by the DNA vaccine. Thus, DNA immunization may offer an attractive alternative strategy against leishmaniasis. We present here the current status of vaccine development against leishmaniasis. 相似文献
5.
Summary. Trypanosomatids depend on spermidine for growth and survival. Consequently, enzymes involved in spermidine synthesis and utilization,
i.e. arginase, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (AdoMetDC), spermidine synthase, trypanothione synthetase (TryS), and trypanothione reductase
(TryR), are promising targets for drug development. The ODC inhibitor α-difluoromethylornithine (DFMO) is about to become
a first-line drug against human late-stage gambiense sleeping sickness. Another ODC inhibitor, 3-aminooxy-1-aminopropane (APA),
is considerably more effective than DFMO against Leishmania promastigotes and amastigotes multiplying in macrophages. AdoMetDC inhibitors can cure animals infected with isolates from
patients with rhodesiense sleeping sickness and leishmaniasis, but have not been tested on humans. The antiparasitic effects
of inhibitors of polyamine and trypanothione formation, reviewed here, emphasize the relevance of these enzymes as drug targets.
By taking advantage of the differences in enzyme structure between parasite and host, it should be possible to design new
drugs that can selectively kill the parasites. 相似文献
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Sagar BM Rentala S Gopal PN Sharma S Mukhopadhyay A 《Biochemical and biophysical research communications》2006,350(4):1000-1005
To test the hypothesis that extracellular matrix (ECM) components maintain stem cell property, murine bone marrow (BM) cells were expanded in fibronectin and laminin coated plate in the presence of cytokines. We observed significant phenotypic and functional improvement of expanded cells. In 10 days, 800-fold expansion of colony-forming unit-granulocyte erythrocyte monocyte megakaryocyte (CFU-GEMM) was observed in the cultured cells. No apparent activation of cell cycle was observed, but CD29 and very late antigen-4 (VLA-4) expression was increased, as compared to the normal BM cells. A fraction of the expanded cells became verapamil sensitive, suggesting upregulation of multi-drug resistant gene(s), as found in the primitive hematopoietic stem cells (HSCs). Competitive repopulation assay confirmed that HSCs compartment was amplified during culture. Overall, our study clearly demonstrated that ex vivo culture of murine HSCs in the presence of fibronectin and laminin resulted in expansion of primitive stem cells and improvement in the marrow engraftibility. 相似文献
8.
Protozoan parasites of the genus Leishmania are important human pathogens that cycle between an extracellular promastigote stage residing in the sandflies and an intracellular amastigote stage colonizing the phagolysosomal compartment of the mammalian macrophages. Here, we used the isobaric tagging method to quantify the global proteomic differences between the promastigotes and the intracellular amastigotes of three different Leishmania donovani clones derived from the THP-1 human macrophage cell line. We identified a substantial number of differentially modulated proteins involved in nutrient acquisition and energy metabolism, cell motility and cytoskeleton, transport, cell signaling and stress response. Proteins involved in vesicular trafficking and endocytosis like the rab7 GTP binding protein, GTP-binding proteins of the Ras superfamily and developmentally regulated GTP-binding protein 1 revealed enhanced expression and also a putative dynein heavy chain protein was found to be up-regulated in the amastigotes and it probably has a role in cargo transport inside the vesicles. Significantly, in the amastigotes the expression of a protein involved in glucose transport was increased eight to fifteen-fold, whereas concentrations of several proteins associated with cell motility and cytoskeleton were reduced. Thus, the quantitative proteomic analysis of L. donovani isolates sheds light on some novel proteins that may have a role in Leishmania differentiation and intracellular survival. 相似文献
9.
A. I. Bhat P. S. Hareesh R. Madhubala 《Journal of plant biochemistry and biotechnology.》2005,14(1):37-40
The coat protein gene of an isolate of Cucumber mosaic virus (CMV) associated with stunted disease affecting black pepper plant was cloned and sequenced. The coat protein gene comprised of 657 nucleotides encoding a protein of 218 amino acids. Sequence analysis showed that the gene was most closely related to CMV infecting Egyptian henbane plant in India, the member of subgroup I of CMV. The amino acid sequence identity with members of subgroup I was 92-99% while that with members of subgroup II was 77–79%. On the basis of sequence homology, it is concluded that CMV infecting black pepper in India is a strain of CMV belonging to subgroup I. 相似文献
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