Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 84
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Metabolomics ; 16(2): 20, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980950

RESUMO

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder. Hyperandrogenism (HA) and insulin resistance (IR) are two important pathogenic factors. OBJECTIVE: We aimed to investigate the inherent disturbed metabolic profiles for women with HA or IR in PCOS as well as discover diagnostic biomarkers. METHODS: A total of 286 subjects were recruited for the study. They constituted the following groups: healthy women (C), those with HA (B1), those with IR but not obese (B2) and obese women with IR (B3) in PCOS. Nine cross-comparisons with PCOS were performed to characterize metabolic disturbances. Serum metabolomic profiles were determined by gas chromatography-mass spectrometry. RESULTS AND CONCLUSION: We found a total of 59 differential metabolites. 28 metabolites for B1 vs C, 32 for B2 vs C and 25 for B3 vs C were discovered. Among them, palmitic acid, cholesterol, myo-inositol, D-allose, 1,5-anhydro-D-sorbitol, 1-monopalmitin, 1-monostearin, glycerol 1-phosphate, malic acid and citric acid, were the common differential metabolites among B1 vs C, B2 vs C and B3 vs C, which related to biosynthesis of unsaturated fatty acids, citrate cycle etc. Besides, 9-biomarker panel can diagnose well between HA and IR in PCOS. They provided areas under the receiver operating characteristic curve of 0.8511 to 1.000 in the discovery phase, and predictive values of 90% to 92% in the validation set. The result indicated that the differential metabolites can reflect the underlying mechanism of PCOS and serve as biomarkers for complementary diagnosis of HA and IR in PCOS.

2.
J Proteome Res ; 19(2): 864-872, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917576

RESUMO

Ankylosing spondylitis (AS) is a systemic, chronic, and inflammatory rheumatic disease that affects 0.2% of the population. Current diagnostic criteria for disease activity rely on subjective Bath Ankylosing Spondylitis Disease Activity Index scores. Here, we aimed to discover a panel of serum protein biomarkers. First, tandem mass tag (TMT)-based quantitative proteomics was applied to identify differential proteins between 15 pooled active AS and 60 pooled healthy subjects. Second, cohort 1 of 328 humans, including 138 active AS and 190 healthy subjects from two independent centers, was used for biomarker discovery and validation. Finally, biomarker panels were applied to differentiate among active AS, stable AS, and healthy subjects from cohort 2, which enrolled 28 patients with stable AS, 26 with active AS, and 28 healthy subjects. From the proteomics study, a total of 762 proteins were identified and 46 proteins were up-regulated and 59 proteins were down-regulated in active AS patients compared to those in healthy persons. Among them, C-reactive protein (CRP), complement factor H-related protein 3 (CFHR3), α-1-acid glycoprotein 2 (ORM2), serum amyloid A1 (SAA1), fibrinogen γ (FG-γ), and fibrinogen ß (FG-ß) were the most significantly up-regulated inflammation-related proteins and S100A8, fatty acid-binding protein 5 (FABP5), and thrombospondin 1 (THBS1) were the most significantly down-regulated inflammation-related proteins. From the cohort 1 study, the best panel for the diagnosis of active AS vs healthy subjects is the combination of CRP and SAA1. The area under the receiver operating characteristic (ROC) curve was nearly 0.900, the sensitivity was 0.970%, and the specificity was 0.805% at a 95% confidence interval from 0.811 to 0.977. Using 0.387 as the cutoff value, the predictive values reached 92.00% in the internal validation set (62 with active AS vs 114 healthy subjects) and 97.50% in the external validation phase (40 with active AS vs 40 healthy subjects). From the cohort 2 study, a panel of CRP and SAA1 can differentiate well among active AS, stable AS, and healthy subjects. For active AS vs stable AS, the area under the ROC curve was 0.951, the sensitivity was 96.43%, the specificity was 88.46% at a 95% confidence interval from 0.891 to 1, and the coincidence rate was 92.30%. For stable AS vs healthy humans, the area under the ROC curve was 0.908, the sensitivity was 89.29%, the specificity was 78.57% at a 95% confidence interval from 0.836 to 0.980, and the coincidence rate was 83.93%. For active AS vs healthy subjects, the predictive value was 94.44%. The results indicated that the CRP and SAA1 combination can potentially diagnose disease status, especially for active or stable AS, which will be conducive to treatment recommendation for patients with AS.

3.
J Pharm Biomed Anal ; 179: 112984, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31759764

RESUMO

Xiao-Ai-Jie-Du decoction (XAJDD), a traditional Chinese medicine formula, has long been used for the treatment of hepatocarcinoma, gastric cancer and colorectal cancer. It is composed of six herbal medicines, including Scutellariae Barbatae Herba, Pseudostellariae Radix, Ophiopogonis Radix, Cremastrae Pseudobulbus, Curcumae Rhizoma and Akebiae Fructus. Despite the in-depth study on its pharmacological effects on cancer prevention and treatment, the comprehensive analysis of the chemical components and the absorbed bioactive constituents are not well studied. Thus, an ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was established to detect and identify the chemical constituents in XAJDD. The absorbed components and metabolites after oral administration of XAJDD in rats were also studied. In total, 102 components were identified or tentatively characterized in XAJDD, including 30 flavonoids, 19 triterpenoids, 12 organic acids, 9 steroidal saponins, 9 cyclic peptides, 7 phenanthrenes, 5 amino acids, 3 alkaloids and 8 other compounds. After analysing the metabolites in rat plasma and urine after oral administration of XAJDD, a total of 70 compounds were identified, including 15 primary components and 55 metabolites, and metabolic pathways, including hydrogenation, hydroxylation, methylation, sulfonation, and glucuronidation were evaluated. Among these, methylation and glucuronidation were the main metabolic pathways. In conclusion, the developed UHPLC-Q-TOF-MS method with high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents of XAJDD in vitro and characterizing the primary components and their metabolites in vivo; moreover, the results will provide essential data for further studying the relationship between the chemical components and pharmacological activity of XAJDD.

4.
J Hematol Oncol ; 12(1): 109, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651345

RESUMO

The original article [1] contained an error in Fig. 7c whereby the same flow image was accidentally misused for the second and fourth group.

5.
JCI Insight ; 4(22)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31647783

RESUMO

Glomerular disease is characterized by proteinuria and glomerulosclerosis, two pathologic features caused by podocyte injury and mesangial cell activation, respectively. However, whether these two events are linked remains elusive. Here, we report that sonic hedgehog (Shh) is the mediator that connects podocyte damage to mesangial activation and glomerulosclerosis. Shh was induced in glomerular podocytes in various models of proteinuric chronic kidney diseases (CKD). However, mesangial cells in the glomeruli, but not podocytes, responded to hedgehog ligand. In vitro, Shh was induced in podocytes after injury and selectively promoted mesangial cell activation and proliferation. In a miniorgan culture of isolated glomeruli, Shh promoted mesangial activation but did not affect the integrity of podocytes. Podocyte-specific ablation of Shh in vivo exhibited no effect on proteinuria after adriamycin injection but hampered mesangial activation and glomerulosclerosis. Consistently, pharmacologic blockade of Shh signaling decoupled proteinuria from glomerulosclerosis. In humans, Shh was upregulated in glomerular podocytes in patients with CKD and its circulating level was associated with glomerulosclerosis but not proteinuria. These studies demonstrate that Shh mechanistically links podocyte injury to mesangial activation in the pathogenesis of glomerular diseases. Our findings also illustrate a crucial role for podocyte-mesangial communication in connecting proteinuria to glomerulosclerosis.

6.
Plant Physiol ; 181(3): 1223-1238, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31515447

RESUMO

In flowering plants, the tapetum cells in anthers undergo programmed cell death (PCD) at the late meiotic stage, providing nutrients for further development of microspores, including the formation of the pollen wall. However, the molecular basis of tapetum PCD remains elusive. Here we report a tapetum PCD-related mutant in rice (Oryza sativa), earlier degraded tapetum 1 (edt1), that shows complete pollen abortion associated with earlier-than-programmed tapetum cell death. EDT1 encodes a subunit of ATP-citrate lyase (ACL), and is specifically expressed in the tapetum of anthers. EDT1 localized in both the nucleus and the cytoplasm as observed in rice protoplast transient assays. We demonstrated that the A and B subunits of ACL interacted with each other and might function as a heteromultimer in the cytoplasm. EDT1 catalyzes the critical steps in cytosolic acetyl-CoA synthesis. Our data indicated a decrease in ATP level, energy charge, and fatty acid content in mutant edt1 anthers. In addition, the genes encoding secretory proteases or lipid transporters, and the transcription factors known to regulate PCD, were downregulated. Our results demonstrate that the timing of tapetum PCD must be tightly regulated for successful pollen development, and that EDT1 is involved in the tapetum PCD process. This study furthers our understanding of the molecular basis of pollen fertility and fecundity in rice and may also be relevant to other flowering plants.

7.
FASEB J ; 33(11): 12576-12587, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31461626

RESUMO

Acute kidney injury (AKI) is a devastating condition with high morbidity and mortality. AKI is characterized by tubular injury, inflammation, and vascular impairment. However, the role of interstitial fibroblasts in the pathogenesis of AKI is largely unknown. Here, we show that fibroblasts were activated, as defined by vimentin expression, at 1 h after AKI triggered by ischemia-reperfusion injury (IRI). They rapidly entered the cell cycle with Ki-67-positive staining, which started at 1 h and peaked at 12 h after IRI, whereas tubular cell proliferation peaked at 3 d. The trigger for such an early activation of fibroblasts was identified as sonic hedgehog (Shh), which was rapidly induced in renal tubules and could target interstitial fibroblasts. Tubule-specific knockout of Shh in mice inhibited fibroblast activation and aggravated kidney injury and functional decline after IRI. Likewise, pharmacologic inhibition of Shh signaling with cyclopamine also hindered fibroblast activation and exacerbated kidney damage. These studies uncover that tubule-derived Shh triggers the early activation of fibroblasts, which is required for kidney repair and regeneration. Our findings for the first time illustrate a previously unrecognized importance of interstitial fibroblasts in conferring renal protection in AKI.-Zhou, D., Fu, H., Liu, S., Zhang, L., Xiao, L., Bastacky, S. I., Liu, Y. Early activation of fibroblasts is required for kidney repair and regeneration after injury.

8.
Am J Transl Res ; 11(7): 4139-4150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396324

RESUMO

Cellular adhesion-mediated drug resistance (CAM-DR) occurs frequently in patients with relapsed or refractory multiple myeloma (MM). Elucidating the mechanism underlying CAM-DR and developing the corresponding treatment may prove to be promising for the clinical management of MM. Bruton's tyrosine kinase (BTK) has been attracting attention in relation to MM progression and drug resistance. BTK was reported to be associated with cell surface CXCR4, a classic cell adhesion molecule and homing factor. However, the exact association between BTK and CAM-DR in MM remains elusive. In this study, we demonstrated that promoting BTK expression induced MM cell adherence to the extracellular matrix (ECM) and stromal cells in vitro and in vivo, and that CAM-DR could be reversed by separating MM cells from ECM or stromal cells. Enhancing BTK expression levels increased CXCR4 expression in MM cells. In addition, BTK may bind directly with CXCR4 and prevent its ubiquitination-induced degradation. Finally, a BTK inhibitor exerted synergistic therapeutic effects with bortezomib in a 5TMM3VT MM mouse model. These findings revealed a novel role of BTK in CAM-DR and may provide a promising approach to MM treatment.

9.
Cell Res ; 29(10): 820-831, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31444468

RESUMO

The transient elevation of cytoplasmic calcium is essential for pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). However, the calcium channels responsible for this process have remained unknown. Here, we show that rice CDS1 (CELL DEATH and SUSCEPTIBLE to BLAST 1) encoding OsCNGC9, a cyclic nucleotide-gated channel protein, positively regulates the resistance to rice blast disease. We show that OsCNGC9 mediates PAMP-induced Ca2+ influx and that this event is critical for PAMPs-triggered ROS burst and induction of PTI-related defense gene expression. We further show that a PTI-related receptor-like cytoplasmic kinase OsRLCK185 physically interacts with and phosphorylates OsCNGC9 to activate its channel activity. Our results suggest a signaling cascade linking pattern recognition to calcium channel activation, which is required for initiation of PTI and disease resistance in rice.

10.
Int Immunopharmacol ; 75: 105768, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31382166

RESUMO

Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) which has become a global public health problem. Limonin is a triterpenoid extracted from citrus which possesses the capacities to against inflammations and cell apoptosis. However, the efficacy and the underlying mechanisms of limonin in the treatment of UC remain unclear. In this study, we first investigated the therapeutic effects of limonin on dextran sodiumsulfate (DSS)-induced UC in vivo by examining the changes of disease activity index (DAI), the colon length, the colon histology, and cyto/chemokine levels. We found that limonin markedly reduced DAI, intestinal damages, and the levels of pro-inflammatory cytokines, such as TNF-α and IL-6. In vitro, limonin significantly repressed the productions of pro-inflammatory cytokines in cultured normal colonic epithelial cells. Mechanistically, we demonstrated that limonin improved the prognosis of UC mainly through downregulating p-STAT3/miR-214 levels. Collectively, our results suggested that limonin was a novel therapeutic agent and it was expected to be translated into the clinic to improve the prognosis of UC.

11.
Eur J Pharmacol ; 859: 172525, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31288005

RESUMO

Emodin can effectively inhibit colorectal cancer cells, but the mechanism remains elusive. This study analyzed the changes of VEGFR2 signaling pathways in patients with colorectal cancer and the effects of emodin on HCT116 cells and xenograft tumor model. The expression levels of VEGFR2, PI3K, and p-AKT in colorectal cancer tissue samples were significantly higher than those in adjacent normal ones. Docking simulation confirmed that emodin bound the hydrophobic pocket and partially overlapped with the binding sites of VEGFR2, thus disrupting VEGFR2 dimerization. Western blotting further confirmed that emodin significantly inhibited the expression of VEGFR2, and reduced the expressions of PI3K and p-AKT in HCT116 cells. Furthermore, it suppressed the growth, adhesion and migration of HCT116 cells. In addition, emodin inhibited the tumor growth in xenograft model and the expressions of VEGFR2, PI3K and p-AKT in vivo. In conclusion, emodin suppressed the growth of colorectal cancer cells by inhibiting VEGFR2, as a potential candidate for therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/patologia , Emodina/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Antineoplásicos/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Emodina/metabolismo , Células HCT116 , Humanos , Masculino , Camundongos , Simulação de Acoplamento Molecular , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Conformação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Nanoscale ; 11(27): 12905-12914, 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31250871

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIONs) have a history of clinical use as contrast agents in T2 weighted MRI, though relatively low T2 relaxivity has caused them to fall out of favor as new faster MRI techniques have gained prominence. We demonstrate that SPIONs coated with a monolayer of succinylated heparin (Su-HP-SPIONs) exhibit over four-fold increased T2 relaxivity (460 mM-1 s-1) as compared to the clinically approved SPION-based contrast agent Feridex (98.3 mM-1 s-1) due to greatly increased water interaction from increased hydrophilicity and thinner coating as supported by our proposed parametric model. In vivo, the performance increase of the Su-HP-SPIONs in T2 MRI imaging of xenograft tumors is ten-fold that of our in-house synthesized Feridex analogue, due to better tumor localization from the smaller size imparted by the thinner coating. In addition to these significantly improved magnetic properties, the succinylated heparin coating also exhibits favorable synthetic reproducibility, solution stability, and biocompatibility. These findings demonstrate the untapped potential of SPIONs as possible high performance clinical T2 contrast agents.


Assuntos
Meios de Contraste , Dextranos , Heparina , Imagem por Ressonância Magnética , Nanopartículas de Magnetita , Ácido Succínico , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacologia , Dextranos/química , Dextranos/farmacologia , Heparina/química , Heparina/farmacologia , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Camundongos , Camundongos Nus , Ácido Succínico/química , Ácido Succínico/farmacologia
13.
Talanta ; 199: 164-169, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30952241

RESUMO

A novel metal-enhanced chemiluminescence (MEC) signal tag was designed. By combining with a disposable immunosensor chip, an ultrasensitive immunoassay method was proposed for detection of C-reactive protein (CRP), an essential cerebrovascular disease marker. Two kinds of silver nanoparticle (AgNP) probes, DNA-hemin/DNA-A/biotin-DNA modified AgNPs (Probe A) and DNA-hemin/DNA-B modified AgNPs (Probe B) were prepared respectively. The MEC signal tag was formed by the link of Probe A and Probe B through the hybridization of DNA-A and DNA-B. The formed AgNP hybrid probes brought excellent CL signal amplification, due to the increased content of hemin molecules and the great MEC effect. The AgNP hybrid probes can be bound to the biotinylated antibody of sandwich immunocomplex for immunoassay of CRP. Under optimal conditions, the method showed a wide detection range of 7 × 10-7 to 0.07 mg mL-1 and a detection limit down to 0.05 ng mL-1. The results obtained with clinical serum samples were in acceptable agreement with reference values. The AgNP hybrid probes as well as the MEC-based immunoassay method showed great potentials in early clinical diagnosis of cerebrovascular disease.


Assuntos
Proteína C-Reativa/análise , Corantes Fluorescentes/química , Luminescência , Nanopartículas Metálicas/química , Prata/química , Biotina/química , DNA/química , Hemina/química , Humanos , Tamanho da Partícula , Propriedades de Superfície
14.
J Hematol Oncol ; 12(1): 23, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832689

RESUMO

BACKGROUND: The expression of CYP4Z1 and the pseudogene CYP4Z2P has been shown to be specifically increased in breast cancer by our group and others. Additionally, we previously revealed the roles of the competitive endogenous RNA (ceRNA) network mediated by these genes (ceRNET_CC) in breast cancer angiogenesis, apoptosis, and tamoxifen resistance. However, the roles of ceRNET_CC in regulating the stemness of breast cancer cells and the mechanisms through which ceRNET_CC is regulated remain unclear. METHODS: Transcriptional factor six2, CYP4Z1-3'UTR, and CYP4Z2P-3'UTR were stably overexpressed or knocked down in breast cancer cells via lentivirus infection. ChIP-sequencing and RNA-sequencing analysis were performed to reveal the mechanism through which ceRNET_CC is regulated and the transcriptome change mediated by ceRNET_CC. Clinical samples were used to validate the correlation between six2 and ceRNET_CC. Finally, the effects of the six2/ceRNET_CC axis on the stemness of breast cancer cells and chemotherapy sensitivity were evaluated by in vitro and in vivo experiments. RESULTS: We revealed that ceRNET_CC promoted the stemness of breast cancer cells. Mechanistically, six2 activated ceRNET_CC by directly binding to their promoters, thus activating the downstream PI3K/Akt and ERK1/2 pathways. Finally, we demonstrated that the six2/ceRNET_CC axis was involved in chemoresistance. CONCLUSIONS: Our results uncover the mechanism through which ceRNET_CC is regulated, identify novel roles for the six2/ceRNET_CC axis in regulating the stemness of breast cancer cells, and propose the possibility of targeting the six2/ceRNET_CC axis to inhibit breast cancer stem cell (CSC) traits.

15.
Plant Cell Rep ; 38(2): 183-194, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30499032

RESUMO

KEY MESSAGE: GARS encodes an enzyme catalyzing the second step of purine nucleotide biosynthesis and plays an important role to maintain the development of chloroplasts in juvenile plants by affecting the expression of plastid-encoded genes. A series of rice white striped mutants were previously described. In this research, we characterized a novel gars mutant with white striped leaves at the seedling stage. By positional cloning, we identified the mutated gene, which encodes a glycinamide ribonucleotide synthetase (GARS) that catalyzes the second step of purine nucleotide biosynthesis. Thylakoid membranes were less abundant in the albinic sectors of mutant seedling leaves compared to the wild type. The expression levels of genes involved in chlorophyll synthesis and photosynthesis were changed. Contents of ATP, ADP, AMP, GTP and GDP, which are crucial for plant growth and development, were decreased in the mutant seedlings. Complementation and CrispR tests confirmed the role of the GARS allele, which was expressed in all rice tissues, especially in the leaves. GARS protein displayed a typical chloroplast location pattern in rice protoplasts. Our results indicated that GARS was involved in chloroplast development at early leaf development by affecting the expression of plastid-encoded genes.


Assuntos
Carbono-Nitrogênio Ligases/genética , Cloroplastos/metabolismo , Genes de Plantas , Oryza/enzimologia , Oryza/genética , Nucleotídeos de Purina/biossíntese , Vias Biossintéticas/genética , Carbono-Nitrogênio Ligases/metabolismo , Clorofila/biossíntese , Cloroplastos/ultraestrutura , Regulação da Expressão Gênica de Plantas , Mutação/genética , Fenótipo , Fotossíntese/genética , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
16.
J Agric Food Chem ; 66(40): 10388-10393, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30260225

RESUMO

Limonin is a triterpenoid in citrus seeds, which has significant biological activities. However, the metabolic profile of limonin has not been fully understood. To expound its metabolism in vivo and in vitro, the metabolites of limonin was studied by rat liver microsomes, urine, and bile. High-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was used for identification. Among the metabolites, the structures of M1 and M3 were confirmed by chemical synthesis and nuclear magnetic resonance spectra analysis. Our results indicated that reduction and hydrolysis were the two major pathways during limonin metabolism in vivo and in vitro. The results from this work are valuable and important for understanding the metabolic process of limonin.


Assuntos
Bile/metabolismo , Limoninas/metabolismo , Microssomos Hepáticos/metabolismo , Urina/química , Animais , Bile/química , Biotransformação , Cromatografia Líquida de Alta Pressão , Feminino , Limoninas/química , Masculino , Espectrometria de Massas , Microssomos Hepáticos/química , Estrutura Molecular , Ratos , Ratos Sprague-Dawley
18.
J Exp Bot ; 69(16): 3949-3961, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29893948

RESUMO

Chloroplasts play an essential role in plant growth and development, and cold conditions affect chloroplast development. Although many genes or regulators involved in chloroplast biogenesis and development have been isolated and characterized, many other components affecting chloroplast biogenesis under cold conditions have not been characterized. Here, we report the functional characterization of a white stripe leaf 5 (wsl5) mutant in rice. The mutant develops white-striped leaves during early leaf development and is albinic when planted under cold stress. Genetic and molecular analysis revealed that WSL5 encodes a novel chloroplast-targeted pentatricopeptide repeat protein. RNA sequencing analysis showed that expression of nuclear-encoded photosynthetic genes in the mutant was significantly repressed, and expression of many chloroplast-encoded genes was also significantly changed. Notably, the wsl5 mutation causes defects in editing of rpl2 and atpA, and splicing of rpl2 and rps12. wsl5 was impaired in chloroplast ribosome biogenesis under cold stress. We propose that the WSL5 allele is required for normal chloroplast development in maintaining retrograde signaling from plastids to the nucleus under cold stress.


Assuntos
Cloroplastos/metabolismo , Resposta ao Choque Frio , Oryza/fisiologia , Proteínas de Plantas/fisiologia , Estresse Fisiológico , Alelos , Clonagem Molecular , Regulação para Baixo , Genes de Plantas , Íntrons , Oryza/genética , Oryza/metabolismo , Fotossíntese/genética , Proteínas de Plantas/genética , Plastídeos/genética , Edição de RNA , Processamento de RNA , Transdução de Sinais
19.
Science ; 360(6393): 1130-1132, 2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29880691

RESUMO

Selfish genetic elements are pervasive in eukaryote genomes, but their role remains controversial. We show that qHMS7, a major quantitative genetic locus for hybrid male sterility between wild rice (Oryza meridionalis) and Asian cultivated rice (O. sativa), contains two tightly linked genes [Open Reading Frame 2 (ORF2) and ORF3]. ORF2 encodes a toxic genetic element that aborts pollen in a sporophytic manner, whereas ORF3 encodes an antidote that protects pollen in a gametophytic manner. Pollens lacking ORF3 are selectively eliminated, leading to segregation distortion in the progeny. Analysis of the genetic sequence suggests that ORF3 arose first, followed by gradual functionalization of ORF2 Furthermore, this toxin-antidote system may have promoted the differentiation and/or maintained the genome stability of wild and cultivated rice.


Assuntos
Instabilidade Genômica , Oryza/genética , Infertilidade das Plantas , Locos de Características Quantitativas , Sequências Repetitivas de Ácido Nucleico , Cruzamentos Genéticos , Evolução Molecular , Células Germinativas Vegetais , Hibridização Genética , Fases de Leitura Aberta/genética , Pólen/genética
20.
Front Plant Sci ; 9: 782, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29946330

RESUMO

The chloroplast is a self-independent organelle and contains its own transcription and translation systems. The establishment of genetic systems is vital for normal plant growth and development. We isolated a rice zebra leaf 16 (zl16) mutant derived from rice cultivar 9311. The zl16 mutant showed chlorotic abnormalities in the transverse sectors of the young leaves of seedlings. The use of transmission electron microscopy (TEM) demonstrated that dramatic defects occurred in variegated zl16 leaves during the early development of a chloroplast. Map-based cloning revealed that ZL16 encodes a ß-hydroxyacyl-ACP dehydratase (HAD) involved in de novo fatty acid synthesis. Compared with the wild type, a missense mutation (Arg164Trp) in the zl16 mutant was identified, which significantly reduced enzymatic activity and altered the three-dimensional modeling structure of the putative protein. ZL16 was ubiquitously expressed in various plant organs, with a pronounced level in the young leaf. A subcellular localization experiment indicated that ZL16 was targeted in the chloroplast. Furthermore, we analyzed the expression of some nuclear genes involved in chloroplast development, and found they were altered in the zl16 mutant. RNA-Seq analysis indicated that some genes related to cell membrane constituents were downregulated in the mutant. An in vivo metabolic assay revealed that the total fatty acid content in the mutant was significantly decreased relative to the wild type. Our results indicate that HAD is essential for the development of chloroplasts by regulating the synthesis of fatty acids in rice.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA