Ornithine Decarboxylase Gene Research Articles

Anti-inflammatory and antitumor promotional effects of a novel urinary metabolite, 3',4'-didemethylnobiletin, derived from nobiletin

We reported previously that 3',4'-didemethylnobiletin (DDMN) is the major metabolite of nobiletin in mouse urine. In this study, we examined DDMN's molecular mechanism of action and its anti-inflammatory and antitumor properties. We demonstrated that topical application of DDMN effectively inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated transcription of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and ornithine decarboxylase (ODC) messenger RNA and protein expression in mouse skin. Pretreatment with DDMN has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappa B (NF-kappaB) subunit. DDMN also reduced DNA binding by blocking phosphorylation of inhibitor kappaB (IkappaB) alpha and p65 and caused subsequent degradation of IkappaBalpha. DDMN inhibited TPA-induced phosphorylation and nuclear translocation of the signal transducer and activator of transcription 3. Moreover, DDMN suppressed TPA-induced activation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt and protein kinase C that are upstream of NF-kappaB and activator protien-1. We also found that DDMN significantly inhibited TPA-induced mouse skin inflammation by decreasing inflammatory parameters. Furthermore, DDMN significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 weeks. Presented data for the first time reveal that DDMN is an effective antitumor agent that functions by downregulating inflammatory iNOS, COX-2 and ODC gene expression in mouse skin. It is suggested that DDMN is a novel functional agent capable of preventing inflammation-associated tumorigenesis.

IL-4 and IL-13 upregulate ornithine decarboxylase expression by PI3K and MAP kinase pathways in vascular smooth muscle cells

Ornithine decarboxylase (ODC) is the first and rate-controlling enzyme in the synthesis of polyamines, which are essential for normal cell growth. We have previously demonstrated that IL-4 and IL-13 can stimulate rat aortic smooth muscle cell (RASMC) proliferation. The objective of this study was to determine whether IL-4 and IL-13 induce cell proliferation by upregulating ODC expression in RASMC. The results revealed that incubation of RASMC with IL-4 and IL-13 for 24 h caused four- to fivefold induction of ODC catalytic activity. The increased ODC catalytic activity was attributed to the increased expression of ODC mRNA. Moreover, these observations were paralleled by increased production of polyamines. We further investigated the signal transduction pathways responsible for ODC induction by IL-4 and IL-13. The data illustrated that PD-98059, a MEK (MAPK kinase) inhibitor, LY-294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, and H-89, a protein kinase A (PKA) inhibitor, substantially decreased the induction of ODC catalytic activity and ODC mRNA expression induced by IL-4 and IL-13, suggesting positive regulation of the ODC gene by ERK, PI3K, and PKA pathways. Interestingly, dexamethasone, a known inhibitor of cell proliferation, completely abrogated the response of RASMC to IL-4 and IL-13. Furthermore, the inhibition of ODC by these inhibitors led to the reduced production of polyamines and decreased DNA synthesis as monitored by [(3)H]thymidine incorporation. Our data indicate that upregulation of ODC by IL-4 and IL-13 might play an important role in the pathophysiology of vascular disorders characterized by excessive smooth muscle growth.

Characterization of a Second Ornithine Decarboxylase Isolated from Morganella morganii

The genes involved in the putrescine formation by Morganella morganii were investigated because putrescine is an indicator of food process deterioration. We report here on the existence of a new gene for ornithine decarboxylase (ODC) in M. morganii. The sequenced 5,311-bp DNA region showed the presence of four complete and one partial open reading frame. Putative functions have been assigned to several gene products by sequence comparison with the proteins included in the databases. The third open reading frame (speC) encoded a 722–amino acid protein showing 70.9% identity to the M. morganii ODC previously characterized (SpeF).The speC gene has been expressed in Escherichia coli, resulting in ODC activity. The presence of a functional promoter (PspeC) located upstream of speC has been demonstrated. Quantitative real-time reverse transcription PCR assay was used to quantify expression of both M. morganii ODC-encoding genes, speC and speF, under different growth conditions. This assay allows us to identify SpeF as the inducible M. morganii ODC, since it was highly expressed in the presence of ornithine.

Role of ornithine decarboxylase in breast cancer

Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis that decarboxylates ornithine to putrescine, has become a promising target for cancer research. The aim of this study is to investigate the role of ODC in breast cancer. We detected expression of ODC in breast cancer tissues and four breast cancer cell lines, and transfected breast cancer cells with an adenoviral vector carrying antisense ODC (rAd-ODC/Ex3as) and examined their growth and migration. ODC was overexpressed in breast cancer tissues and cell lines compared with non-tumor tissues and normal breast epithelial cells, and there was a positive correlation between the level of ODC mRNA and the staging of tumors. The expression of ODC correlated with cyclin D1, a cell cycle protein, in synchronized breast cancer MDA-MB-231 cells. Gene transfection of rAd-ODC/Ex3as markedly down-regulated expression of ODC and cyclin D1, resulting in suppression of proliferation and cell cycle arrest at G0-G1 phase, and the inhibition of colony formation, an anchorage-independent growth pattern, and the migratory ability of MDA-MB-231 cells. rAd-ODC/Ex3as also markedly reduced the concentration of putrescine, but not spermidine or spermine, in MDA-MB-231 cells. The results suggested that the ODC gene might act as a prognostic factor for breast cancer and it could be a promising therapeutic target.

Disruption of the MYC transcriptional function by a small-molecule antagonist of MYC/MAX dimerization

Inhibition of MYC/MAX dimerization by a small-molecule antagonist (IIA6B17) has been shown to interfere with MYC-induced transformation of chick embryo fibroblasts, suggesting that the functional inhibitors of the MYC family of oncoproteins have potential as therapeutic agents. In the present study, a functional MYC reporter gene assay has been developed, using a luciferase gene construct under the control of the ornithine decarboxylase (ODC) gene promoter. This luciferase gene construct has been stably transfected into the MYCN amplified neuroblastoma cell line (NGP) and MYCC-overexpressed neuroepithelioma cell line (NB100). After exposure of the cell lines to IIA6B17 for 24 h, a significant reduction of luciferase activity was only observed in the NB100 cells, with IC50 values of approximately 28+/-9 microM, indicating that IIA6B17 has cell line-specific activity which may be selective for individual members of the MYC family.

Phylogeny and classification of the Old World Emberizini (Aves, Passeriformes)

The phylogeny of the avian genus Emberiza and the monotypic genera Latoucheornis, Melophus and Miliaria (collectively the Old World Emberizini), as well as representatives for the New World Emberizini, the circumpolar genera Calcarius and Plectrophenax and the four other generally recognized tribes in the subfamily Emberizinae was estimated based on the mitochondrial cytochrome b gene and introns 6–7 of the nuclear ornithine decarboxylase (ODC) gene. Our results support monophyly of the Old World Emberizini, but do not corroborate a sister relationship to the New World Emberizini. Calcarius and Plectrophenax form a clade separated from the other Emberizini. This agrees with previous studies, and we recommend the use of the name Calcariini. Latoucheornis, Melophus and Miliaria are nested within Emberiza, and we therefore propose they be synonymized with Emberiza. Emberiza is divided into four main clades, whose relative positions are uncertain, although a sister relation between a clade with six African species and one comprising the rest of the species (30, all Palearctic) is most likely. Most clades agree with traditional, morphology-based, classifications. However, four sister relationships within Emberiza, three of which involve the previously recognized Latoucheornis, Melophus and Miliaria, are unpredicted, and reveal cases of strong morphological divergence. In contrast, the plumage similarity between adult male Emberiza (formerly Latoucheornis) siemsseni and the nominate subspecies of the New World Junco hyemalis is shown to be the result of parallel evolution. A further case of parallel plumage evolution, between African and Eurasian taxa, is pointed out. Two cases of discordance between the mitochondrial and nuclear data with respect to branch lengths and genetic divergences are considered to be the result of introgressive hybridization.

Regulatory effects of corticosterone on ornithine decarboxylase activity during liver regeneration in rats

The regulation of ornithine decarboxylase (ODC) gene expression and enzyme activity by corticosterone during rat liver regeneration induced by partial hepatectomy (PH) was evaluated. Bilateral adrenalectomies were performed on ether-anesthetized rats 3 days before PH. Corticosterone in sesame oil was injected subcutaneously to adrenalectomized rats. ODC mRNA, ODC protein and enzyme activity were detected by in situ hybridization, Western blot and high performance liquid chromatography (HPLC), respectively. The ODC mRNA levels, protein accumulation and enzyme activity were lower in the intact liver compared to the regenerating liver. After PH, mRNA levels were remarkably enhanced in all groups and peaked at 5 h post-PH, and presented a persistent increase only in adrenalectomy rats during the regeneration process. Corticosterone treatment resulted in a dose-dependent decrease in ODC mRNA content after 5 h post-PH. ODC protein accumulation in adrenalectomy rats was higher than that in sham-adrenalectomy rats, but it decreased in corticosterone-treated (10 mg/kg) rats until 24 h post-PH, with a strong decline seen in 40 mg/kg corticosterone-treated rats. ODC activity was rapidly promoted, and the highest levels were observed at 6 h after PH in all groups. After corticosterone treatment, the activities declined significantly at 6 h post-PH, with the lowest value found in the 40 mg/kg group. Corticosterone treatment results in dose-dependent decreases in ODC mRNA and enzyme protein both in the intact liver and the regenerating liver. The change in ODC activity is partially related to alterations of ODC mRNA and protein accumulation.

Combined IFN-γ and retinoic acid treatment targets the N-Myc/Max/Mad1 network resulting in repression of N-Myc target genes in MYCN-amplified neuroblastoma cells

The MYCN protooncogene is involved in the control of cell proliferation, differentiation, and survival of neuroblasts. Deregulation of MYCN by gene amplification contributes to neuroblastoma development and is strongly correlated to advanced disease and poor outcome, emphasizing the urge for new therapeutic strategies targeting MYCN function. The transcription factor N-Myc, encoded by MYCN, regulates numerous genes together with its partner Max, which also functions as a cofactor for the Mad/Mnt family of Myc antagonists/transcriptional repressors. We and others have previously reported that IFN-gamma synergistically potentiates retinoic acid (RA)-induced sympathetic differentiation and growth inhibition in neuroblastoma cells. This study shows that combined treatment of MYCN-amplified neuroblastoma cells with RA+IFN-gamma down-regulates N-Myc protein expression through increased protein turnover, up-regulates Mad1 mRNA and protein, and reduces N-Myc/Max heterodimerization. This results in a shift of occupancy at the ornithine decarboxylase N-Myc/Mad1 target promoter in vivo from N-Myc/Max to Mad1/Max predominance, correlating with histone H4 deacetylation, indicative of a chromatin structure typical of a transcriptionally repressed state. This is further supported by data showing that RA+IFN-gamma treatment strongly represses expression of N-Myc/Mad1 target genes ornithine decarboxylase and hTERT. Our results suggest that combined IFN-gamma and RA signaling can form a basis for new therapeutic strategies targeting N-Myc function for patients with high-risk, MYCN-amplified neuroblastoma.

Sequence-specific oxidative base modifications in hypoxia-inducible genes

Reactive oxygen species associated with hypoxic signaling in pulmonary arterial endothelial cells (PAECs) oxidatively modify specific nucleotides in the hypoxic response element (HRE) of the VEGF gene ( FASEB J. 19:387–394; 2005). In this study, we determined in PAECs if hypoxia caused genome-wide oxidative modifications or if they were restricted to the promoters of genes differentially regulated by hypoxia. Comet assays indicated that there were no differences between normoxic and hypoxic PAECs in terms of global DNA damage. However, a simple PCR-based method involving DNA amplification before and after treatment with formamidopyrimidine DNA glycosylase (Fpg), a bacterial DNA repair enzyme that cleaves at sites of purine base oxidation, revealed that hypoxia caused modifications in the HREs of the hypoxia-inducible VEGF, HO-1, and ET-1 genes which coincided with accumulation of their respective mRNA transcripts. Promoter sequences not involved with hypoxic induction and coding regions of these genes failed to display Fpg-sensitive sites. Oxidative modifications also were not detected in sequences of the hypoxia down-regulated ornithine decarboxylase and TFAM genes or the constitutively expressed β-actin gene. These findings show that hypoxia-mediated oxidative DNA modifications cluster in functionally relevant promoter sequences in hypoxia-inducible genes and suggest that such oxidative modifications may be biologically significant.

Trypanosoma cruzi as a model system to study the expression of exogenous genes coding for polyamine biosynthetic enzymes. Induction of DFMO resistance in transgenic parasites

Trypanosoma cruzi, the etiologic agent of Chagas' disease, is a polyamine auxotroph organism because its genome contains neither ornithine decarboxylase (ODC) nor arginine decarboxylase (ADC) genes, presumably lost during evolution. After transformation with a recombinant plasmid bearing the complete coding region of Crithidia fasciculata ODC gene, the transgenic parasites were able to synthesize putrescine and simultaneously became susceptible to α-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. We have studied the emergence of DFMO-resistant T. cruzi after one-step selection of ODC-transformed parasites cultivated in the presence of high levels of the drug (5 mM). Our results have indicated a duplication of the ODC gene copy number in the drug-resistant cell line. The ODC transcripts and the corresponding translation products showed very significant increases (about 7- and 25-fold, respectively) in DFMO-resistant parasites, while the ODC enzymatic activity was 5 times higher than in drug-sensitive T. cruzi. The unequal increases of ODC protein and enzymatic activity in DFMO-resistant protozoa strongly suggest that in addition to gene amplification and enhanced transcription and translation, the assembly of ODC polypeptide chains into dimeric active enzyme molecules might also contribute to regulate the development of DFMO resistance.

Polyamines are required for expression of Toll-like receptor 2 modulating intestinal epithelial barrier integrity

The Toll-like receptors (TLRs) allow mammalian intestinal epithelium to detect various microbes and activate innate immunity after infection. TLR2 and TLR4 have been identified in intestinal epithelial cells (IECs) as fundamental components of the innate immune response to bacterial pathogens, but the exact mechanism involved in control of TLR expression remains unclear. Polyamines are implicated in a wide variety of biological functions, and regulation of cellular polyamines is a central convergence point for the multiple signaling pathways driving different epithelial cell functions. The current study determined whether polyamines regulate TLR expression, thereby modulating intestinal epithelial barrier function. Depletion of cellular polyamines by inhibiting ornithine decarboxylase (ODC) with alpha-difluoromethylornithine decreased levels of TLR2 mRNA and protein, whereas increased polyamines by ectopic overexpression of the ODC gene enhanced TLR2 expression. Neither intervention changed basal levels of TLR4. Exposure of normal IECs to low-dose (5 microg/ml) LPS increased ODC enzyme activity and stimulated expression of TLR2 but not TLR4, while polyamine depletion prevented this LPS-induced TLR2 expression. Decreased TLR2 in polyamine-deficient cells was associated with epithelial barrier dysfunction. In contrast, increased TLR2 by the low dose of LPS enhanced epithelial barrier function, which was abolished by inhibition of TLR2 expression with specific, small interfering RNA. These results indicate that polyamines are necessary for TLR2 expression and that polyamine-induced TLR2 activation plays an important role in regulating epithelial barrier function.

Adenovirus-mediated Expression of both Antisense Ornithine Decarboxylase and S-adenosylmethionine Decarboxylase Inhibits Lung Cancer Cell Growth

Polyamine biosynthesis is controlled primarily by ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC). Antisense sequences of ODC and AdoMetDC genes were cloned into an adenoviral vector (named Ad-ODC-AdoMetDCas). To evaluate the effects of recombinant adenovirus Ad-ODC-AdoMetDCas that can simultaneously express both antisense ODC and AdoMetDC, the human lung cancer cell line A-549 was infected with Ad-ODC-AdoMetDCas or the control vector. Viable cell counting, determination of polyamine concentrations, cell cycle analysis, and Matrigel invasion assays were carried out to assess the properties of tumor growth and invasiveness. Our study showed that adenovirus-mediated antisense ODC and AdoMetDC expression inhibits tumor cell growth through blocking the polyamine synthesis pathway. Tumor cells were arrested at the G1 phase after gene transfer and the invasiveness was reduced. It suggested that the recombinant adenovirus Ad-ODC-AdoMetDCas might be a new anticancer reagent in the treatment of lung cancers.

Construction and analysis of Leishmania tarentolae transgenic strains free of selection markers

The trypanosomatid protozoan Leishmania tarentolae has been extensively used as a model system for studying causative agents of several tropical diseases and more recently as a host for recombinant protein production. Here we analyze the rates of partial or complete deletions of expression cassettes integrated into small ribosomal RNA and tubulin gene clusters as well as into ornithine decarboxylase gene of L. tarentolae. In approximately 60% of cases gene conversion was responsible for the deletion while in the rest of the cases deletion occurred within the expression cassette. We used this observation to design constitutive and inducible expression vectors that could be stably integrated into the genome and subsequently depleted of the antibiotic resistance genes using thymidine kinase or bleomycin resistance genes as negative selection markers. This enabled us to obtain L. tarentolae strains containing constitutive or inducible markerless expression cassettes. Analysis of the markerless strains demonstrated that although stability varied among clones some were stable for as many as 200 generations. We expect that this approach will be useful for the construction of strains carrying multiple expression cassettes for analysis of trypanosomatid pathogenicity mechanisms and overexpression of multi-subunit protein complexes for biochemical and structural studies.

Androgen receptor and c-Myc transcription factors as putative partners in the in vivo cross-talk between androgen receptor-mediated and c-Met-mediated signalling pathways.

Cross-talk between two signal transduction pathways leads to a negative regulation of androgen-induced ornithine decarboxylase (ODC) gene expression in the mouse kidney. One pathway is triggered by testosterone via the intracellular androgen receptor, AR, and the other is induced by antifolate CB 3717 or folate via hepatocyte growth factor and its cell membrane receptor c-Met. Here we report the studies of the expression of AR and c-Myc transcription factors involved in ODC transactivation. Administration of CB 3717 or folate decreased the expression of AR. In contrast, testosterone did not modify AR mRNA content but augmented the AR protein. Furthermore, we demonstrate that administration of folate, but not testosterone, increases c-Myc transcript and protein level. We also document that activation of both examined pathways does not decrease the testosterone-induced AR protein level, but markedly increases c-Myc protein which is nearly 2-fold up-regulated compared to its level evoked solely by testosterone. We suspect that this pronounced increase of c-Myc protein might have functional consequences mirrored by down-regulated expression of AR target genes, among them ODC.

P53-Dependent NDRG1 expression induces inhibition of intestinal epithelial cell proliferation but not apoptosis after polyamine depletion

Normal intestinal mucosal growth requires polyamines that regulate expression of various genes involved in cell proliferation, growth arrest, and apoptosis. Our previous studies have shown that polyamine depletion stabilizes p53, resulting in inhibition of intestinal epithelial cell (IEC) proliferation, but the exact downstream targets of induced p53 are still unclear. The NDRG1 (N-myc downregulated gene-1) gene encodes a growth-related protein, and its transcription can be induced in response to stress. The current study tests the hypothesis that induced p53 inhibits IEC proliferation by upregulating NDRG1 expression following polyamine depletion. Depletion of cellular polyamines by inhibiting ornithine decarboxylase (ODC) with alpha-difluoromethylornithine not only induced p53 but also increased NDRG1 transcription as indicated by induction of the NDRG1 promoter activity and increased levels of NDRG1 mRNA and protein, all of which were prevented by using specific p53 siRNA and in cells with a targeted deletion of p53. In contrast, increased levels of cellular polyamines by ectopic expression of the ODC gene decreased p53 and repressed expression of NDRG1. Consistently, polyamine depletion-induced activation of the NDRG1-promoter was decreased when p53-binding sites within the NDRG1 proximal promoter region were deleted. Ectopic expression of the wild-type NDRG1 gene inhibited DNA synthesis and decreased final cell numbers regardless of the presence or absence of endogenous p53, whereas silencing NDRG1 promoted cell growth. However, overexpression of NDRG1 failed to directly induce cell death and to alter susceptibility to apoptosis induced by tumor necrosis factor-alpha/cycloheximide. These results indicate that NDRG1 is one of the direct mediators of induced p53 following polyamine depletion and that p53-dependent NDRG1 expression plays a critical role in the negative control of IEC proliferation.

The effects of genetic manipulation of putrescine biosynthesis on transcription and activities of the other polyamine biosynthetic enzymes1

We have studied the effects of overproduction of putrescine (Put) via transgenic expression of a mouse ornithine decarboxylase (ODC) gene on the expression of native genes for four enzymes involved in polyamine biosynthesis in hybrid poplar (Populus nigra×maximowiczii) cells. An examination of the transcript levels of arginine decarboxylase (ADC), ODC, S‐adenosylmethionine decarboxylase (SAMDC) and spermidine synthase (SPDS), as well as their enzyme activities (except SPDS), showed that the expression of different members of the SAMDC and SPDS gene families was affected differently in response to alteration of the cellular Put content. It was further observed that there was a strong correlation between transcript levels and the activity of the respective enzyme in the cells. Moreover, there was no feedback inhibition of the expression of the native ODC or the ADC genes or their enzyme activities by increased Put in the cells.

Association of a Polymorphism in the Ornithine Decarboxylase Gene with Whole Blood Polyamine Concentrations in a Non-smoking Healthy Population

Ornithine decarboxylase (ODC) is the rate-limiting key enzyme in the biosynthesis of polyamines which have been confirmed to possess potent antioxidant and antiglycating properties. The aim of the present study was to examine the relationship of the ODC polymorphism and circulating whole blood polyamine concentrations. The study subjects were non-smoking, healthy men (n = 30) and women (n = 30) aged 55–69 years with equal numbers of AA, GA, and GG genotypes of the ODC gene, who were randomly recruited from 607 health checkup examinees. The whole blood polyamines (spermidine and spermine) were determined by high-performance liquid chromatography and were adjusted for hematocrit. The difference in the adjusted polyamines across theODC gene was statistically tested using analysis of covariance. Women homozygous for the A-allele showed significantly higher spermidine levels than those with other genotypes. No such association was found among men, and spermine showed no association with the ODC genotype. In conclusion, the ODC polymorphism is significantly associated with whole blood polyamines in women. The ODC gene seems to be expressed more actively among female A-allele homozygotes than women carrying the G-allele.

No association between Helicobacter pylori seropositivity and ornithine decarboxylase (ODC) A317G polymorphism, and no modification by NAD(P)H:qinone oxidoreductase 1 (NQO1) C609T.

Our previous epidemiologic study reported that NAD(P)H:quinone oxidoreductase 1 (NQO1) 609C/C with full enzyme activity was a high risk genotype for Helicobacter pylori (H. pylori) seropositivity. Since NQO1 stabilizes ornithine decarboxylase (ODC), which attenuates the innate immune response through elevated polyamines, ODC functional polymorphisms may also influence H. pylori seropositivity. This study aimed to examine the association with ODC A317G polymorphism, as well as the modification by NQO1 C609T. The two polymorphisms were determined by polymerase chain reaction with confronting two-pair primers (PCR-CTPP) among 465 health checkup examinees in Nagoya. The ODC A317G genotype frequency was 35.9% for A/A, 49.3% for A/G, and 14.8% for G/G. The sex-age-adjusted odds ratio (OR) of the ODC gene for H. pylori seropositivity was not significant (OR = 1.09 for G/A and OR = 1.02 for G/G, relative to A/A). Among subjects with any NQO1 genotype, no association was observed between the ODC ploymorphism and H. pylori seropositivity. Results of the present study did not support the hypothesis that the different genetic traits in the ODC-polyamine pathway are associated with susceptibility to persistent H. pylori infection. The higher frequency of the ODC 317A allele in the Japanese population than that in the Caucasian population is firstly reported. The genetic traits through the ODC-polyamine pathway will be further investigated.

Targeting polyamines ofAspergillusnidulansby siRNA specific to fungal ornithine decarboxylase gene

Aspergillus nidulans is a filamentous, ubiquitous and opportunistic pathogenic fungus, which causes fatal invasive aspergillosis among immunocompromised patients. As a prelude to the investigations on the possible control of human fungal diseases by selective targeting of fungal polyamines that are essential for fungal growth and development by RNAi strategy, we have examined the effect of siRNA specific to a key polyamine biosynthesis gene ornithine decarboxylase (ODC) on the in vitro germinating spores of A. nidulans to assess the ability of RNA species to induce RNA-mediated gene silencing. The present findings show that siRNA can cause specific silencing effect, with the phenotypic consequences leading to significant reduction in mycelial growth, target mRNA titers and cellular polyamine concentrations. This study suggests that fungal polyamine biosynthetic genes, particularly ODC may be targeted for the control of fungal infections in humans and crop plants. To the best of our knowledge, this is the first demonstration of up-take of siRNA by germinating fungal spores from culture medium, and attempt to target a vital pathway in fungal pathogens for their control.

The protective effect of aspirin against colorectal adenoma is modified by polymorphisms of the ornithine decarboxylase (ODC) gene,

The protective effect of aspirin against colorectal adenoma is modified by polymorphisms of the ornithine decarboxylase (ODC) gene,