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1.
Chem Res Toxicol ; 32(9): 1893-1899, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31433626

RESUMO

In previous studies, we showed that the topical application of dibenzo[a,l]pyrene (DB[a,l]P), also known as dibenzo[def,p]chrysene, to the oral cavity of mice induced oral squamous cell carcinoma. We also showed that dA and dG adducts likely account for most of the mutagenic activity of DB[a,l]P in the oral tissues in vivo. Here we report for the first time that the oral treatment of lacI mice with a combination of tobacco smoke carcinogens, DB[a,l]P and N'-nitrosonornicotine (NNN), induces a higher fraction of mutations than expected from a simple sum of their induced individual mutation fractions, and a change in the mutational profile compared with that expected from the sum of the individual agents. The mutational profile of the combination of agents resembled that of the P53 gene in human head and neck cancers more than that of either of the individual agents, in that the percentage of the major class of mutations (GC > AT transitions) is similar to that seen in the P53 gene. A preliminary study was performed to understand the origin of the unexpected mutagenesis observations by measuring specific DNA adducts produced by both NNN and DB[a,l]P in human oral leukoplakia cells. No significant differences in the expected and observed major adduct levels from either agent were observed between individual or combined treatments, suggesting that additional adducts are important in mutagenesis induced by the mixture. Taken together, the above observations support the use of this animal model not only to investigate tobacco smoke-induced oral cancer but also to study chemoprevention.

2.
J Proteome Res ; 18(9): 3461-3469, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31369706

RESUMO

We reported that breast density (BD) was inversely correlated with the plasma level of DHA in postmenopausal obese, but not in nonobese, women given Lovaza (n-3FA). To identify protein biomarkers for the possible differential effect of n-3FA on BD between obese and nonobese women, an iTRAQ method was performed to analyze plasma from obese and lean women at each time point (baseline, 12 and 24-months, n = 10 per group); 173 proteins with >95% confidence (Unuses Score >1.3 and local false discovery rate estimation <5%) were identified. Comparative analysis between various groups identified several differentially expressed proteins (hemopexin precursor, vitamin D binding protein isoform 1 precursor [VDBP], fibronectin isoform 10 precursor [FN], and α-2 macroglobulin precursor [A2M]). Western blot analysis was performed to verify the differential expression of proteins in the iTRAQ study, and those found to be altered in a tumor protective fashion by an n-3FA rich diet in our previous preclinical study; gelsolin, VDBP, and FN were altered by n-3FA in a manner consistent with reduction in inflammation in obese women. To test the impact of our findings on breast cancer risk reduction by n-3FA, a posthoc analysis revealed that n-3FA administration reduced BD selectively in obese postmenopausal women.

3.
New Phytol ; 223(1): 246-260, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30802963

RESUMO

Appropriate regulation of crop seed germination is of significance for agriculture production. In this study, we show that TaJAZ1, most closely related to Arabidopsis JAZ3, negatively modulates abscisic acid (ABA)-inhibited seed germination and ABA-responsive gene expression in bread wheat. Biochemical interaction assays demonstrate that the C-terminal part containing the Jas domain of TaJAZ1 physically interacts with TaABI5. Similarly, Arabidopsis jasmonate-ZIM domain (JAZ) proteins also negatively modulate ABA responses. Further we find that a subset of JAZ proteins could interact with ABI5 using the luciferase complementation imaging assays. Choosing JAZ3 as a representative, we demonstrate that JAZ3 interacts with ABI5 in vivo and represses the transcriptional activation activity of ABI5. ABA application could abolish the enrichment of JAZ proteins in the ABA-responsive gene promoter. Furthermore, we find that ABA application could induce the expression of jasmonate (JA) biosynthetic genes and then increase the JA concentrations partially dependent on the function of ABI5, consequently leading to the degradation of JAZ proteins. This study sheds new light on the crosstalk between JA and ABA in modulating seed germination in bread wheat and Arabidopsis.

4.
J Plant Physiol ; 234-235: 117-132, 2019 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784850

RESUMO

The GASA (GA-stimulated Arabidopsis) gene family is highly specific to plants, signifying a crucial role in plant growth and development. Herein, we retrieved 119 GASA genes in 10 different plant species in two major lineages (monocots and eudicots). Further, in the phylogenetic tree we classified these genes into four well-conserved subgroups. All the proteins contain a conserved GASA domain with similar characteristics and a highly specific 12-cysteine residue of the C-terminus position. According to the global microarray data and qRT-PCR based analysis, the OsGASA gene family was dominantly expressed in the seedling and transition phase of floral stages. Despite this, OsGASA genes profoundly contribute to rice grain size and length, whereas the highest abundance of transcript level was noticed in stage-2 (Inf 6, 3.0-cm-long spikelet) and stage-3 (Inf 7, 5.0-cm-long spikelet) under GA treatment during panicle formation. Additionally, the maximum expression level of these genes was recorded in response to GA and ABA in young seedlings. Further, in response to abiotic stresses, OsGASA1/8/10 was up- regulated by salt, OsGASA2/5/7 by drought, OsGASA3/6 by cold, and OsGASA4/9 by heat stress. With the exception of OsGASA4, the higher transcription levels of all the other GASA genes were induced by Cd and Cr metal stresses (8-10 fold changes) at various time points. Finally, the GO ontology analysis of GASAs revealed the biological involvement in the GA-mediated signaling pathway and abiotic stresses. Prominently, most of these proteins are localized in cellular components such as the cell wall and extracellular region, where the molecular functions such as ATP binding and protein binding were observed. These results imply that GASAs are significantly involved in rice panicle developmental stages, responses to external stimuli, and hormones.


Assuntos
Giberelinas/metabolismo , Família Multigênica , Oryza/genética , Proteínas de Plantas/fisiologia , Sequência de Aminoácidos , Arabidopsis , Proteínas de Arabidopsis , Cromossomos de Plantas , Simulação por Computador , Expressão Gênica , Metais Pesados , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Filogenia , Regiões Promotoras Genéticas , Estresse Fisiológico
5.
BMC Genomics ; 20(1): 27, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626335

RESUMO

BACKGROUND: B-box (BBX) proteins play important roles in plant growth regulation and development including photomorphogenesis, photoperiodic regulation of flowering, and responses to biotic and abiotic stresses. RESULTS: In the present study we retrieved total 131 BBX members from five Poaceae species including 36 from maize, 30 from rice, 24 from sorghum, 22 from stiff brome, and 19 from Millet. All the BBX genes were grouped into five subfamilies on the basis of their phylogenetic relationships and structural features. The expression profiles of 12 OsBBX genes in different tissues were evaluated through qRT-PCR, and we found that most rice BBX members showed high expression level in the heading stage compared to seedling and booting stages. The expression of OsBBX1, OsBBX2, OsBBX8, OsBBX19, and OsBBX24 was strongly induced by abiotic stresses such as drought, cold and salt stresses. Furthermore, the expression of OsBBX2, OsBBX7, OsBBX17, OsBBX19, and OsBBX24 genes was up-regulated under GA, SA and MeJA hormones at different time points. Similarly, the transcripts level of OsBBX1, OsBBX7, OsBBX8, OsBBX17, and OsBBX19 genes were significantly affected by heavy metals such as Fe, Ni, Cr and Cd. CONCLUSION: Change in the expression pattern of BBX members in response to abiotic, hormone and heavy metal stresses signifies their potential roles in plant growth and development and in response to multivariate stresses. The findings suggest that BBX genes could be used as potential genetic markers for the plants, particularly in functional analysis and determining their roles under multivariate stresses.


Assuntos
Proteínas de Transporte/genética , Evolução Molecular , Poaceae/genética , Estresse Fisiológico/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genoma de Planta/genética , Metais/toxicidade , Família Multigênica/genética , Desenvolvimento Vegetal/genética , Proteínas de Plantas/genética , Poaceae/crescimento & desenvolvimento , Plântula/genética , Plântula/crescimento & desenvolvimento , Fatores de Transcrição/genética
6.
Chem Res Toxicol ; 31(11): 1111-1118, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30260214

RESUMO

Ovarian cancer ranked second in incidence among gynecologic cancers, but it causes more deaths than any other gynecologic cancer; at present there is no curative treatment beyond surgery. Animal models that employ carcinogens found in the human environment can provide a realistic platform to understand the mechanistic basis for disease development and to design rational chemopreventive/therapeutic strategies. We and others have shown that the administration of the environmental pollutant and tobacco smoke constituent dibenzo[ def,p]chrysene (DBP) to mice by several routes of exposure can induce tumors in multiple sites including the ovary. In the present study we compared, for the first time, the tumorigenicity and DNA damage induced by DBP and its metabolites DBP-dihydrodiol (DBPDHD) and DBP-dihydrodiol epoxide (DBPDE) in the mouse ovary. Compounds were dissolved in dimethyl sulfoxide (DMSO) as the vehicle and administered by topical application into the mouse oral cavity three times per week for 38 weeks. No tumors were observed in mice treated with DMSO. At equal dose (24 nmol/30 µL DMSO), the incidence of ovarian tumors induced by DBPDHD was higher (60.7%), although not significantly, than that induced by DBP (44.8%). Similarly the levels of DNA damage induced by DBPDHD in the ovary were higher than those observed with DBP. We did not observe any histological abnormality in the ovary of mice treated with DBPDE, which is consistent with lack of DNA damage. Our results suggested that both DBP and DBPDHD can be metabolized in the mouse ovary leading to the formation of DBPDE that can damage DNA, which is a prerequisite step in the initiation stage of carcinogenesis.

7.
Front Plant Sci ; 9: 906, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30083172

RESUMO

As the key producers of reactive oxygen species (ROS), NADPH oxidases (NOXs), also known as respiratory burst oxidase homologs (RBOHs), play crucial roles in various biological processes in plants with considerable evolutionary selection and functional diversity in the entire terrestrial plant kingdom. However, only limited resources are available on the phylogenesis and functions of this gene family in wheat. Here, a total of 46 NOX family genes were identified in the wheat genome, and these NOXs could be classified into three subgroups: typical TaNOXs, TaNOX-likes, and ferric reduction oxidases (TaFROs). Phylogenetic analysis indicated that the typical TaNOXs might originate from TaFROs during evolution, and the TaFROs located on Chr 2 might be the most ancient forms of TaNOXs. TaNOXs are highly expressed in wheat with distinct tissue or organ-specificity and stress-inducible diversity. A large-scale expression and/or coexpression analysis demonstrated that TaNOXs can be divided into four functional groups with different expression patterns under a broad range of environmental stresses. Different TaNOXs are coexpressed with different sets of other genes, which widely participate in several important intracellular processes such as cell wall biosynthesis, defence response, and signal transduction, suggesting their vital but diversity of roles in plant growth regulation and stress responses of wheat.

8.
Molecules ; 23(7)2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021984

RESUMO

BBX proteins play important roles in regulating plant growth and development including photomorphogenesis, photoperiodic regulation of flowering, and responses to biotic and abiotic stresses. At present, the genomes of seven Rosaceae fruit species have been fully sequenced. However, little is known about the BBX gene family and their evolutionary history in these Rosaceae species. Therefore, in this study total, 212 BBX genes were investigated from seven Rosaceae species (67 from Malus × domestica, 40 from Pyruscommunis, 22 from Rosa Chinesis, 20 from Prunuspersica, 21 from Fragariavesca, 22 from Prunusavium, and 20 from Rubusoccidentalis). The chemical properties, gene structures, and evolutionary relationships of the BBX genes were also studied. All the BBX genes were grouped into six subfamilies on the basis of their phylogenetic relationships and structural features. Analysis of gene structure, segmental and tandem duplication, gene phylogeny, and tissue-specific expression with the ArrayExpress database showed their diversification in function, quantity, and structure. The expression profiles of 19 MdBBX genes in different tissues were evaluated through qRT-PCR. These genes showed distinct transcription level among the tested tissues (bud, flower, fruit, stem, and leaf). Moreover, expression patterns of 19 MdBBX genes were examined during flowering induction time under flowering-related hormones and treatments (GA3, 6-BA, and sucrose). The expressions of the candidates BBX genes were affected and showed diverse expression profile. Furthermore, changes in response to these flowering-related hormones and treatment specifying their potential involvement in flowering induction. Based on these findings, BBX genes could be used as potential genetic markers for the growth and development of plants particularly in the area of functional analysis, and their involvement in flower induction in fruit plants.


Assuntos
Regulação da Expressão Gênica de Plantas/fisiologia , Genoma de Planta , Malus , Família Multigênica , Proteínas de Plantas , Fatores de Transcrição , Malus/genética , Malus/metabolismo , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
9.
Molecules ; 23(5)2018 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-29757203

RESUMO

The ferric reduction oxidase (FRO) gene family is involved in various biological processes widely found in plants and may play an essential role in metal homeostasis, tolerance and intricate signaling networks in response to a number of abiotic stresses. Our study describes the identification, characterization and evolutionary relationships of FRO genes families. Here, total 50 FRO genes in Plantae and 15 ‘FRO like’ genes in non-Plantae were retrieved from 16 different species. The entire FRO genes have been divided into seven clades according to close similarity in biological and functional behavior. Three conserved domains were common in FRO genes while in two FROs sub genome have an extra NADPH-Ox domain, separating the function of plant FROs. OsFRO1 and OsFRO7 genes were expressed constitutively in rice plant. Real-time RT-PCR analysis demonstrated that the expression of OsFRO1 was high in flag leaf, and OsFRO7 gene expression was maximum in leaf blade and flag leaf. Both genes showed vigorous expressions level in response to different abiotic and hormones treatments. Moreover, the expression of both genes was also substantial under heavy metal stresses. OsFRO1 gene expression was triggered following 6 h under Zn, Pb, Co and Ni treatments, whereas OsFRO7 gene expression under Fe, Pb and Ni after 12 h, Zn and Cr after 6 h, and Mn and Co after 3 h treatments. These findings suggest the possible involvement of both the genes under abiotic and metal stress and the regulation of phytohormones. Therefore, our current work may provide the foundation for further functional characterization of rice FRO genes family.


Assuntos
Biologia Computacional , FMN Redutase/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Metais , Família Multigênica , Reguladores de Crescimento de Planta/farmacologia , Estresse Fisiológico , Transcriptoma , Mapeamento Cromossômico , Biologia Computacional/métodos , Evolução Molecular , Duplicação Gênica , Metais/farmacologia , Anotação de Sequência Molecular , Oryza/genética , Oryza/metabolismo , Filogenia , Espécies Reativas de Oxigênio/metabolismo
10.
Front Plant Sci ; 9: 379, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29662499

RESUMO

NAD(H) and NADP(H) are essential co-enzymes which dominantly control a number of fundamental biological processes by acting as reducing power and maintaining the intracellular redox balance of all life kingdoms. As the only enzymes that catalyze NAD(H) and ATP to synthesize NADP(H), NAD Kinases (NADKs) participate in many essential metabolic reactions, redox sensitive regulation, photosynthetic performance and also reactive oxygen species (ROS) homeostasis of cells and therefore, play crucial roles in both development and stress responses of plants. NADKs are highly conserved enzymes in amino acid sequences but have multiple subcellular localization and diverse functions. They may function as monomers, dimers or multimers in cells but the enzymatic properties in plants are not well elucidated yet. The activity of plant NADK is regulated by calcium/calmodulin and plays crucial roles in photosynthesis and redox co-enzyme control. NADK genes are expressed in almost all tissues and developmental stages of plants with specificity for different members. Their transcripts can be greatly stimulated by a number of environmental factors such as pathogenic attack, irritant applications and abiotic stress treatments. Using transgenic approaches, several studies have shown that NADKs are involved in chlorophyll synthesis, photosynthetic efficiency, oxidative stress protection, hormone metabolism and signaling regulation, and therefore contribute to the growth regulation and stress tolerance of plants. In this review, the enzymatic properties and functional mechanisms of plant NADKs are thoroughly investigated based on literature and databases. The results obtained here are greatly advantageous for further exploration of NADK function in plants.

11.
Plant Cell Environ ; 41(7): 1645-1656, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29645276

RESUMO

Light signals are perceived by multiple photoreceptors that converge to suppress the RING E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) for the regulation of stomatal development. Thus, COP1 is a point of integration between light signaling and stomatal patterning. However, how light signaling is collected into COP1 for the production and spacing of stomata is still unknown. Here, we report that the loss-of-function mutant of ANGUSTIFOLIA3 (AN3) delays asymmetric cell division, which leads to decreased stomatal index. Furthermore, overexpression of AN3 accelerates asymmetric cell division, which results in clusters of stomata. In addition, the stomatal development through AN3 regulation is mediated by light signaling. Finally, we find that an3 is a light-signaling mutant, and that AN3 protein is light regulated. Self-activation by AN3 contributes to the control of AN3 expression. Thus, AN3 is a point of collection between light signaling and stomatal patterning. Target-gene analysis indicates that AN3 is associated with COP1 promoter for the regulation of light-controlling stomatal development. Together, these components for regulating stomatal development form an AN3-COP1-E3 ubiquitin ligase complex, allowing the integration of light signaling into the production and spacing of stomata.

12.
Cancer Prev Res (Phila) ; 11(3): 157-164, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29158340

RESUMO

We previously showed that metabolic activation of the environmental and tobacco smoke constituent dibenzo[a,l]pyrene (DB[a,l]P) to its active fjord region diol epoxide (DB[a,l]PDE) is required to induce DNA damage, mutagenesis, and squamous cell carcinoma (SCC) in the mouse oral cavity. In contrast to procarcinogens, which were employed previously to induce SCC, DB[a,l]PDE does not require metabolic activation to exert its biological effects, and thus, this study was initiated to examine, for the first time, whether black raspberry powder (BRB) inhibits postmetabolic processes, such as DNA damage, mutagenesis, and tumorigenesis. Prior to long-term chemoprevention studies, we initially examined the effect of BRB (5% added to AIN-93M diet) on DNA damage in B6C3F1 mice using LC/MS-MS and on mutagenesis in the lacI gene in the mouse oral cavity. We showed that BRB inhibited DB[a,l]PDE-induced DNA damage (P < 0.05) and mutagenesis (P = 0.053) in the oral cavity. Tumor incidence in the oral cavity (oral mucosa and tongue) of mice fed diet containing 5% BRB was significantly (P < 0.05) reduced from 93% to 66%. Specifically, the incidence of benign tumor was significantly (P < 0.001) reduced from 90% to 31% (62% to 28% in the oral cavity and 28% to 2% in the tongue), a nonsignificant reduction of malignant tumors from 52% to 45%. Our preclinical findings demonstrate for the first time that the chemopreventive efficacy of BRB can be extended to direct-acting carcinogens that do not require phase I enzymes and is not just limited to procarcinogens. Cancer Prev Res; 11(3); 157-64. ©2017 AACR.

13.
Artigo em Inglês | MEDLINE | ID: mdl-29106334

RESUMO

Previously, we showed that oral application of the environmental pollutant dibenzo[a,l]pyrene (DB[a,l]P) induces oral tumors in mice. Thus, in the present investigation we examined the effect of alcohol on DB[a,l]P-induced DNA damage and immune regulation; we showed that alcohol (6.4% v/v in the diet, 35% of Calories) significantly enhanced the levels of (-)-anti-trans-DB[a,l]P-dA while decreased the levels of GSH in the mouse oral tissues. Analysis of RNA expression revealed that DB[a,l]P alone upregulates inflammatory genes while alcohol suppresses several markers of immune surveillance. Collectively, these results suggest that alcohol may enhance oral carcinogenesis induced by DB[a,l]P.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Benzopirenos/metabolismo , Dano ao DNA , Poluentes Ambientais/metabolismo , Boca/metabolismo , Consumo de Bebidas Alcoólicas/imunologia , Alcoolismo , Animais , Carcinogênese , Camundongos , Boca/imunologia , Neoplasias Bucais
14.
Chem Res Toxicol ; 30(12): 2159-2164, 2017 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-29068672

RESUMO

Black raspberries (BRB) have been shown to inhibit carcinogenesis in a number of systems, with most studies focusing on progression. Previously we reported that an anthocyanin-enriched black raspberry extract (BE) enhanced repair of dibenzo-[a,l]-pyrene dihydrodiol (DBP-diol)-induced DNA adducts and inhibited DBP-diol and DBP-diolepoxide (DBPDE)-induced mutagenesis in a lacI rat oral fibroblast cell line, suggesting a role for BRB in the inhibition of initiation of carcinogenesis. Here we extend this work to protection by BE against DNA adduct formation induced by dibenzo-[a,l]-pyrene (DBP) in a human oral leukoplakia cell line (MSK) and to a second carcinogen, UV light. Treatment of MSK cells with DBP and DBPDE led to a dose-dependent increase in DBP-DNA adducts. Treatment of MSK cells with BE after addition of DBP reduced levels of adducts relative to cells treated with DBP alone, and treatment of rat oral fibroblasts with BE after addition of DBPDE inhibited mutagenesis. These observations showed that BE affected repair of DNA adducts and not metabolism of DBP. As a proof of principle we also tested aglycones of two anthocyanins commonly found in berries, delphinidin chloride and pelargonidin chloride. Delphinidin chloride reduced DBP-DNA adduct levels in MSK cells, while PGA did not. These results suggested that certain anthocyanins can enhance repair of bulky DNA adducts. As DBP and its metabolites induced formation of bulky DNA adducts, we investigated the effects of BE on genotoxic effects of a second carcinogen that induces bulky DNA damage, UV light. UV irradiation produced a dose-dependent increase in cyclobutanepyrimidine dimer levels in MSK cells, and post-UV treatment with BE resulted in lower cyclobutanepyrimidine dimer levels. Post-UV treatment of the rat lacI cells with BE reduced UV-induced mutagenesis. Taken together, the results demonstrate that BE extract reduces bulky DNA damage and mutagenesis and support a role for BRB in the inhibition of initiation of carcinogenesis.


Assuntos
DNA/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Leucoplasia Oral/tratamento farmacológico , Extratos Vegetais/farmacologia , Rubus/química , Animais , Benzopirenos/farmacologia , Células Cultivadas , Adutos de DNA/biossíntese , Adutos de DNA/efeitos dos fármacos , Dano ao DNA , Relação Dose-Resposta a Droga , Humanos , Leucoplasia Oral/genética , Leucoplasia Oral/patologia , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ratos , Relação Estrutura-Atividade , Raios Ultravioleta
15.
PLoS One ; 12(10): e0186873, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29073177

RESUMO

Genetic and epigenetic alterations observed at end stage OSCC formation could be considered as a consequence of cancer development and thus changes in normal or premalignant tissues which had been exposed to oral carcinogens such as Dibenzo[def,p]chrysene (DBP) may better serve as predictive biomarkers of disease development. Many types of DNA damage can induce epigenetic changes which can occur early and in the absence of evident morphological abnormalities. Therefore we used ERRBS to generate genome-scale, single-base resolution DNA methylomes from histologically normal oral tissues of mice treated with DBP under experimental conditions known to induce maximum DNA damage which is essential for the development of OSCC induced by DBP in mice. After genome-wide correction, 30 and 48 differentially methylated sites (DMS) were identified between vehicle control and DBP treated mice using 25% and 10% differences in methylation, respectively. RT-PCR was further performed to examine the expressions of nine selected genes. Among them, Fgf3, a gene frequently amplified in head and neck cancer, showed most prominent and significant gene expression change (2.4× increases), despite the hypomethylation of Fgf3 was identified at >10kb upstream of transcription start site. No difference was observed in protein expression between normal oral tissues treated with DBP or vehicle as examined by immunohistochemistry. Collectively, our results indicate that Fgf3 hypomethylation and gene overexpression, but not protein expression, occurred in the early stage of oral carcinogenesis induced by DBP. Thus, Fgf3 hypomethylation may serve as a potential biomarker for early detection of OSCC.


Assuntos
Benzopirenos/toxicidade , Biomarcadores Tumorais/metabolismo , Carcinógenos/toxicidade , Carcinoma de Células Escamosas/diagnóstico , Fator 3 de Crescimento de Fibroblastos/metabolismo , Neoplasias Bucais/diagnóstico , Tabaco/química , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Metilação de DNA , Detecção Precoce de Câncer , Feminino , Camundongos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Reação em Cadeia da Polimerase em Tempo Real
16.
Plant J ; 92(5): 904-923, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28960566

RESUMO

Leaf rolling is considered as one of the most important agronomic traits in rice breeding. It has been previously reported that SEMI-ROLLED LEAF 1 (SRL1) modulates leaf rolling by regulating the formation of bulliform cells in rice (Oryza sativa); however, the regulatory mechanism underlying SRL1 has yet to be further elucidated. Here, we report the functional characterization of a novel leaf-rolling mutant, curled leaf and dwarf 1 (cld1), with multiple morphological defects. Map-based cloning revealed that CLD1 is allelic with SRL1, and loses function in cld1 through DNA methylation. CLD1/SRL1 encodes a glycophosphatidylinositol (GPI)-anchored membrane protein that modulates leaf rolling and other aspects of rice growth and development. The cld1 mutant exhibits significant decreases in cellulose and lignin contents in secondary cell walls of leaves, indicating that the loss of function of CLD1/SRL1 affects cell wall formation. Furthermore, the loss of CLD1/SRL1 function leads to defective leaf epidermis such as bulliform-like epidermal cells. The defects in leaf epidermis decrease the water-retaining capacity and lead to water deficits in cld1 leaves, which contribute to the main cause of leaf rolling. As a result of the more rapid water loss and lower water content in leaves, cld1 exhibits reduced drought tolerance. Accordingly, the loss of CLD1/SRL1 function causes abnormal expression of genes and proteins associated with cell wall formation, cuticle development and water stress. Taken together, these findings suggest that the functional roles of CLD1/SRL1 in leaf-rolling regulation are closely related to the maintenance of cell wall formation, epidermal integrity and water homeostasis.


Assuntos
Parede Celular/fisiologia , Oryza/fisiologia , Epiderme Vegetal/fisiologia , Folhas de Planta/fisiologia , Proteínas de Plantas/fisiologia , Clonagem Molecular , Desidratação/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/metabolismo , Epiderme Vegetal/metabolismo , Proteínas de Plantas/metabolismo , Proteostase , Água/metabolismo
17.
Chem Res Toxicol ; 30(1): 126-144, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-28092946

RESUMO

Worldwide, cancers of the oral cavity and pharynx comprise the sixth most common malignancies. Histologically, more than 90% of oral cancers are squamous cell carcinoma (SCC). Epidemiologic data strongly support the role of exogenous factors such as tobacco, alcohol, and human papilloma virus infection as major causative agents. Avoidance of risk factors has only been partially successful, and survival rates have not improved despite advances in therapeutic approaches. Therefore, new or improved approaches to prevention and/or early detection are critical. Better understanding of the mechanisms of oral carcinogenesis can assist in the development of novel biomarkers for early detection and strategies for disease prevention. Toward this goal, several animal models for carcinogenesis in the oral cavity have been developed. Among these are xenograft, and transgenic animal models, and others employing the synthetic carcinogens such as 7,12-dimethylbenz[a]anthracene in hamster cheek pouch and 4-nitroquinoline-N-oxide in rats and mice. Additional animal models employing environmental carcinogens such as benzo[a]pyrene and N'-nitrosonornicotine have been reported. Each model has certain advantages and disadvantages. Models that (1) utilize environmental carcinogens, (2) reflect tumor heterogeneity, and (3) accurately represent the cellular and molecular changes involved in the initiation and progression of oral cancer in humans could provide a realistic platform. To achieve this goal, we introduced a novel nonsurgical mouse model to study oral carcinogenesis induced by dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and tobacco smoke constituent, and its diol epoxide metabolite (±)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene [(±)-anti-DB[a,l]PDE]. On the basis of a detailed comparison of oral cancer induced by DB[a,l]P with that induced by the other above-mentioned oral carcinogens with respect to dose, duration, species and strain, cellular and molecular targets, and relative carcinogenic potency, our animal model may offer a more realistic platform to study oral carcinogenesis. In this perspective, we also discuss our preclinical studies to demonstrate the potential of black raspberry extracts on the prevention of OSCC. Specifically, we were the first to demonstrate that black raspberry inhibited DB[a,l]P-DNA binding and of particular importance its capacity to enhance the repair of DB[a,l]P-induced bulky lesions in DNA. We believe that the information presented in this perspective will stimulate further research on the impact of environmental carcinogens in the development of oral cancer and may lead to novel strategies toward the control and prevention of this disease.


Assuntos
Carcinógenos/toxicidade , Neoplasias Bucais/prevenção & controle , Extratos Vegetais/farmacologia , Rubus , Ativação Metabólica , Animais , Carcinogênese , Carcinógenos/farmacocinética , Adutos de DNA , Reparo do DNA , Modelos Animais de Doenças , Humanos , Neoplasias Bucais/etiologia , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Mutação , Proteína Supressora de Tumor p53/genética
18.
Rice (N Y) ; 9(1): 37, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27473144

RESUMO

BACKGROUND: Rice leaves are important energy source for the whole plant. An optimal structure will be beneficial for rice leaves to capture light energy and exchange gas, thus increasing the yield of rice. Moderate leaf rolling and relatively erect plant architecture may contribute to high yield of rice, but the relevant molecular mechanism remains unclear. RESULTS: In this study, we identified and characterized a rolling and erect leaf mutant in rice and named it as rel2. Histological analysis showed that the rel2 mutant has increased number of bulliform cells and reduced size of middle bulliform cells. We firstly mapped REL2 to a 35-kb physical region of chromosome 10 by map-based cloning strategy. Further analysis revealed that REL2 encodes a protein containing DUF630 and DUF632 domains. In rel2 mutant, the mutation of two nucleotide substitutions in DUF630 domain led to the loss-of-function of REL2 locus and the function of REL2 could be confirmed by complementary expression of REL2 in rel2 mutant. Further studies showed that REL2 protein is mainly distributed along the plasma membrane of cells and the REL2 gene is relatively higher expressed in younger leaves of rice. The results from quantitative RT-PCR analysis indicated that REL2 functioning in the leaf shape formation might have functional linkage with many genes associated with the bulliform cells development, auxin synthesis and transport, etc. CONCLUSIONS: REL2 is the DUF domains contained protein which involves in the control of leaf rolling in rice. It is the plasma membrane localization and its functions in the control of leaf morphology might involve in multiple biological processes such as bulliform cell development and auxin synthesis and transport.

19.
Cancer Prev Res (Phila) ; 9(8): 704-12, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27267891

RESUMO

Effects of black raspberry (BRB) extract and protocatechuic acid (PCA) on DNA adduct formation and mutagenesis induced by metabolites of dibenzo[a,l]pyrene (DBP) were investigated in rat oral fibroblasts. The DBP metabolites, (±)-anti-11,12-dihydroxy-11,12,-dihydrodibenzo[a,l]pyrene (DBP-diol) and 11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DBPDE) induced dose-dependent DNA adducts and mutations. DBPDE was considerably more potent, whereas the parent compound had no significant effect. Treatment with BRB extract (BRBE) and PCA resulted in reduced DBP-derived DNA adduct levels and reduced mutagenesis induced by DBP-diol, but only BRBE was similarly effective against (DBPDE). BRBE did not directly inactivate DBPDE, but rather induced a cellular response-enhanced DNA repair. When BRBE was added to cells 1 day after the DBP-diol, the BRBE greatly enhanced removal of DBP-derived DNA adducts. As oxidative stress can contribute to several stages of carcinogenesis, BRBE and PCA were investigated for their abilities to reduce oxidative stress in a human leukoplakia cell line by monitoring the redox indicator, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF) in cellular and acellular systems. BRBE effectively inhibited the oxidation, but PCA was only minimally effective against H2DCF. These results taken together provide evidence that BRBE and PCA can inhibit initiation of carcinogenesis by polycyclic aromatic hydrocarbons; and in addition, BRBE reduces oxidative stress. Cancer Prev Res; 9(8); 704-12. ©2016 AACR.


Assuntos
Carcinogênese/efeitos dos fármacos , Adutos de DNA/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Boca/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Rubus/química , Animais , Benzopirenos/toxicidade , Carcinogênese/genética , Carcinógenos/toxicidade , Linhagem Celular Tumoral , Células Epiteliais/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Neoplasias Bucais/prevenção & controle , Mutagênese/efeitos dos fármacos , Neoplasias Faríngeas/prevenção & controle , Ratos , Fatores de Tempo
20.
Int J Mol Sci ; 17(6)2016 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-27240354

RESUMO

NADPH oxidases (NOXs), also known as respiratory burst oxidase homologs (RBOHs), are the major source of reactive oxygen species (ROS), and are involved in many important processes in plants such as regulation of acclimatory signaling and programmed cell death (PCD). Increasing evidence shows that NOXs play crucial roles in plant immunity and their functions in plant immune responses are not as separate individuals but with other signal molecules such as kinases, Rac/Rop small GTPases and hormones, mediating a series of signal transmissions. In a similar way, NOX-mediated signaling also participates in abiotic stress response of plants. We summarized here the complex role and regulation mechanism of NOXs in mediating plant immune response, and the viewpoint that abiotic stress response of plants may be a kind of special plant immunity is also proposed.


Assuntos
NADH NADPH Oxirredutases/metabolismo , Imunidade Vegetal , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Fenômenos Fisiológicos Vegetais , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Estresse Fisiológico
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