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1.
J Hazard Mater ; 466: 133660, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38309160

RESUMO

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used, additive flame retardant that migrates from end-use products, leading to ubiquitous exposure of humans around the world. However, little is known about whether TDCIPP disrupts the physiology of human embryonic cells. Therefore, the objective of this study was to determine whether TDCIPP alters cell viability, cellular metabolism, cytosine methylation, and reactive oxygen species (ROS) levels within human embryonic kidney (HEK293) cells. Relative to vehicle controls, TDCIPP (0.015-0.1225 µM) resulted in a concentration-dependent increase in cell viability, a finding that was driven by an increase in relative ATP abundance. Interestingly, TDCIPP (0.061-0.98 µM) increased the rate of glycolysis - an adaptive mechanism consistent with the Warburg effect exhibited by tumorigenic cells. Moreover, relative to vehicle-treated cells, TDCIPP (0.245-15.63 µM) exposure for 48 h (but not 24 h) resulted in a significant, concentration-dependent decrease in ROS in situ, and TDCIPP (0.245 µM) exposure significantly increased carnosine within the histidine metabolism pathway. However, TDCIPP did not affect global 5-methylcytosine (5-mC) methylation (0.015-15.63 µM), cell membrane integrity (0.061-0.98 µM), nor the abundance of mitochondria (0.061-1.95 µM). Overall, our findings with TDCIPP point to a novel mechanism of action that may be relevant to human embryonic stem cells.


Assuntos
Retardadores de Chama , Fosfatos , Humanos , Compostos Organofosforados , Células HEK293 , Espécies Reativas de Oxigênio/metabolismo , Organofosfatos , Rim/metabolismo
2.
Nat Plants ; 9(11): 1890-1901, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37884654

RESUMO

Plant survival depends on dynamic stress-response pathways in changing environments. To uncover pathway components, we screened an ethyl methanesulfonate-mutagenized transgenic line containing a stress-inducible luciferase construct and isolated a constitutive expression mutant. The mutant is the result of an amino acid substitution in the seventh subunit of the hetero-octameric conserved oligomeric Golgi (COG) complex of Arabidopsis thaliana. Complementation studies verified the Golgi localization of cog7, and stress tests established accelerated dark-induced carbon deprivation/senescence of the mutant compared with wild-type plants. Multiomics and biochemical analyses revealed accelerated induction of protein ubiquitination and autophagy, and a counterintuitive increased protein N-glycosylation in senescencing cog7 relative to wild-type. A revertant screen using the overexpressor (FOX)-hunting system established partial, but notable rescue of cog7 phenotypes by COG5 overexpression, and conversely premature senescence in reduced COG5 expressing lines. These findings identify COG-imposed Golgi functional integrity as a main player in ensuring cellular survival under energy-limiting conditions.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Glicosilação
3.
Nat Prod Res ; 37(17): 2951-2956, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36308292

RESUMO

Scandenin and 4'-O-methylderrone were isolated from the ethanol extract of the roots and dichloromethane extract of the leaves of Deguelia costata (Benth.) A.M.G. Azevedo & R.A. Camargo, respectively. These compounds and their extracts had their antiprotozoal, antibacterial, antifungal, and cytotoxic activities tested. All samples were active for amastigotes of the T. cruzi, with EC50 values varying from 34.5 to 9.8 µg mL-1. The 4'-O-methylderrone and scandenin showed better leishmanicidal action against the promastigote of L. amazonensis, with EC50 of 43.3 and 45.9 µg mL-1, respectively, when compared to their extracts. All extracts and scandenin showed activities against Staphylococcus sp, Bacillus sp, and Candida sp. The compounds did not show cytotoxicity on rat macrophages. As confirmed by spectroscopic analyses, the extracts are rich in phenolics, mainly isoflavonoids. The study of D. costata is a promising strategy for discovering isoflavones and 4-hydroxy-3-phenylcoumarins with antiprotozoal, antibacterial, and antifungal activities.

4.
Sleep Biol Rhythms ; 21(4): 473, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38476187

RESUMO

[This corrects the article DOI: 10.1007/s41105-023-00445-5.].

5.
Sleep Biol Rhythms ; 21(3): 265-277, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38469078

RESUMO

Obstructive Sleep Apnea (OSA) corresponds to episodes of complete or partial upper airway obstruction during sleep. The gold standard for diagnosing OSA is polysomnography; however, metabolomics is an innovative and highly sensitive method that seeks to identify and quantify small molecules in biological systems. Identify the metabolites most frequently associated with obstructive sleep apnea in adults. The search for articles was conducted between October 2020 and August 2021, in electronic databases, such as MEDLINE/PubMed, Scielo, Embase, and Cochrane, through the combination of descriptors: obstructive sleep apnea, metabolomic, adult. This systematic review included all cross-sectional studies published, including human patients aged 18 years or older, of both genders who underwent type I or II polysomnography and metabolomics study. The search strategy selected 3697 surveys, and 4 of them were selected to be a part of this systematic review. Based on the analyzed surveys, it was found that all of them were able to diagnose OSA, reaching a sensitivity of 75-97%, and specificity that ranged from 72 to 100%; besides differentiating patients with OSA (severe, moderate, and mild) from simple snorers with a mean sensitivity of 77.2% and specificity of 66.25%. These findings suggest that, in addition to being used as a screening and diagnostic strategy for OSA, metabolomics has the potential to be used for severity stratification and to monitor the disease's progression.

6.
Rev Paul Pediatr ; 40: e2021013, 2022.
Artigo em Inglês, Português | MEDLINE | ID: mdl-35584416

RESUMO

OBJECTIVE: To systematically establish whether there is an association between polymorphisms and avascular necrosis in patients with sickle cell disease. DATA SOURCE: The review, conducted according to PRISMA guidelines and registered with PROSPERO, was based on research of studies in PubMed, SciELO, LILACS, BVS databases and in the gray literature (Google Scholar and Open Gray) published until June 2020. The STROBE initiative was used to analyze the articles' quality. DATA SYNTHESIS: Ten articles were selected from the databases and two were included through manual search, totaling 12 studies. All samples gathered 2,362 patients. According to STROBE, seven studies fully and/or partially covered more than 70% of the essential items and two studies reached less than 60%, with an overall variation of 86.4-54.5%. The results indicate that polymorphisms in the genes of the bone morphogenetic protein 6 (BMP6), Klotho (KL) and Annexin A2 (ANXA2) may be associated with osteonecrosis in the context of sickle cell disease. Six articles addressed the polymorphism in the MTHFR enzyme gene, but only one found a positive association. Polymorphisms associated with the DARC receptor, the ITGA4 gene, CD36 and thrombophilia protein genes were not associated in any of the studies. CONCLUSIONS: The results indicate that the polymorphisms in BMP6, Klotho and ANXA2 genes may be associated with avascular necrosis in patients with sickle cell disease. However, in order to confirm these genetic changes as risk factors, further studies with greater statistical power and methodological rigor are needed.


Assuntos
Anemia Falciforme , Osteonecrose , Anemia Falciforme/complicações , Anemia Falciforme/genética , Humanos , Osteonecrose/complicações , Osteonecrose/genética , Polimorfismo Genético , Fatores de Risco
7.
Nat Commun ; 13(1): 1275, 2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35277503

RESUMO

The RAP (RNA-binding domain abundant in Apicomplexans) protein family has been identified in various organisms. Despite expansion of this protein family in apicomplexan parasites, their main biological functions remain unknown. In this study, we use inducible knockdown studies in the human malaria parasite, Plasmodium falciparum, to show that two RAP proteins, PF3D7_0105200 (PfRAP01) and PF3D7_1470600 (PfRAP21), are essential for parasite survival and localize to the mitochondrion. Using transcriptomics, metabolomics, and proteomics profiling experiments, we further demonstrate that these RAP proteins are involved in mitochondrial RNA metabolism. Using high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (eCLIP-seq), we validate that PfRAP01 and PfRAP21 are true RNA-binding proteins and interact specifically with mitochondrial rRNAs. Finally, mitochondrial enrichment experiments followed by deep sequencing of small RNAs demonstrate that PfRAP21 controls mitochondrial rRNA expression. Collectively, our results establish the role of these RAP proteins in mitoribosome activity and contribute to further understanding this protein family in malaria parasites.


Assuntos
Malária Falciparum , Ribossomos Mitocondriais , Plasmodium falciparum , Proteínas de Protozoários , Proteínas de Ligação a RNA , Genômica , Humanos , Malária Falciparum/parasitologia , Ribossomos Mitocondriais/metabolismo , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
8.
Rev. Paul. Pediatr. (Ed. Port., Online) ; 40: e2021013, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1376334

RESUMO

Abstract Objective: To systematically establish whether there is an association between polymorphisms and avascular necrosis in patients with sickle cell disease. Data source: The review, conducted according to PRISMA guidelines and registered with PROSPERO, was based on research of studies in PubMed, SciELO, LILACS, BVS databases and in the gray literature (Google Scholar and Open Gray) published until June 2020. The STROBE initiative was used to analyze the articles' quality. Data synthesis: Ten articles were selected from the databases and two were included through manual search, totaling 12 studies. All samples gathered 2,362 patients. According to STROBE, seven studies fully and/or partially covered more than 70% of the essential items and two studies reached less than 60%, with an overall variation of 86.4-54.5%. The results indicate that polymorphisms in the genes of the bone morphogenetic protein 6 (BMP6), Klotho (KL) and Annexin A2 (ANXA2) may be associated with osteonecrosis in the context of sickle cell disease. Six articles addressed the polymorphism in the MTHFR enzyme gene, but only one found a positive association. Polymorphisms associated with the DARC receptor, the ITGA4 gene, CD36 and thrombophilia protein genes were not associated in any of the studies. Conclusions: The results indicate that the polymorphisms in BMP6, Klotho and ANXA2 genes may be associated with avascular necrosis in patients with sickle cell disease. However, in order to confirm these genetic changes as risk factors, further studies with greater statistical power and methodological rigor are needed.


Resumo Objetivo: Estabelecer, de modo sistemático, se existe associação entre polimorfismos e a necrose avascular em pacientes com doença falciforme. Fontes de dados: A revisão, conduzida segundo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) e registrada no International Prospective Register of Systematic Reviews (PROSPERO), foi baseada na busca de estudos nas bases de dados PubMed, Scientific Electronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Biblioteca Virtual em Saúde (BVS) e na literatura cinza (Google Scholar e Open Gray) até junho de 2020. A análise da qualidade dos artigos foi baseada nos critérios do Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). Síntese dos dados: Dez artigos foram selecionados nas bases de dados e dois incluídos por meio da busca manual, totalizando 12 estudos elencados. As amostras resultaram em 2.362 pacientes incluídos. Com base na iniciativa STROBE, sete estudos atenderam total e/ou parcialmente mais de 70% dos itens essenciais e dois atingiram menos que 60% deles, com variação geral de 86,4-54,5%. Os resultados mostram que os polimorfismos nos genes da proteína morfogenética óssea 6 (BMP6), da Klotho (KL) e da Anexina A2 (ANXA2) podem ter associação com osteonecrose no contexto da doença falciforme. Seis artigos estudaram o polimorfismo no gene da enzima MTHFR, mas apenas um obteve associação positiva. Os polimorfismos associados ao receptor DARC, ao gene ITGA4, ao CD36 e aos genes de proteínas trombofílicas não demonstraram associação em nenhum dos estudos. Conclusões: Os polimorfismos nos genes BMP6, KL e ANXA2 estão possivelmente associados com a necrose avascular em indivíduos com doença falciforme. Entretanto, para a confirmação dessas alterações genéticas como fatores de risco, é necessário que mais estudos com maior poder estatístico e com maior rigor metodológico sejam realizados.

9.
Pathogens ; 10(5)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063357

RESUMO

The increasing rates of maternal and congenital syphilis (CS) infections are public health concerns and need further investigation in order to provide better assistance in epidemiological surveillance and new strategies for the assistance and prevention of CS. In December 2011, the Brazilian Ministry of Health (BMH) implemented ordinance number 3.242, reinforced in 2012 by ordinance number 77, aiming to improve the quality of the syphilis diagnosis system using rapid tests. Here, we evaluate the incidence, lethality, and possible factors associated with CS in Salvador, Bahia, in the pre-resolution period (2007 to 2011) and post-resolution (2012 to 2016). An observational, ecological time-series study is conducted using secondary data collected from the National Notifiable Diseases Information System (SINAN). Linear regression analysis to estimate increases or reductions in the mean incidence over time is also performed. A total of 5470 CS cases are analyzed. The incidence ranges from 2.1 cases per 1000 live births in 2007 to 17.1 cases per 1000 live births in 2019, showing a progressive increase in incidence over the years and reduction of lethality in the post-resolution period. The number of CS cases reported prior to the implementation of the ordinances (2007-2011) does not reveal a significant increase in the incidence. However, in the post-ordinances period (2012-2019), there is an average increase of the number of CS cases by three times over the years, with an average increase of 1.8 new cases annually. Our findings highlight the importance of diagnosis and support information in strategies for CS prevention. Furthermore, these data show a positive impact of resolutions on the diagnosis and evolution of the disease.

10.
Br J Haematol ; 192(5): 922-931, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33476407

RESUMO

Sickle cell anaemia (SCA) is a debilitating genetic haemoglobinopathy predominantly affecting the disenfranchised strata of society in Africa and the Americas. The most common pharmacological treatment for this disease is the administration of hydroxycarbamide (HC) for which questions remain regarding its mechanism of action, efficacy and long-term toxicity specifically in paediatric individuals. A multiplatform metabolomics approach was used to assess the metabolome of plasma samples from a population of children and adolescents with SCA with and without HC treatment along with non-SCA individuals. Fifty-three metabolites were identified by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and 1 H nuclear magnetic resonance (NMR) with a predominance of membrane lipids, amino acids and organic acids. The partial least-squares discriminant analysis (PLS-DA) analysis allowed a clear discrimination between the different studied groups, revealing clear effects of the HC treatment in the patients' metabolome including rescue of specific metabolites to control levels. Increased creatine/creatinine levels under HC treatment suggests a possible increase in the arginine pool and increased NO synthesis, supporting existing models for HC action in SCA. The metabolomics results extend the current knowledge on the models for SCA pathophysiology including impairment of Lands' cycle and increased synthesis of sphingosine 1-phosphate. Putative novel biomarkers are suggested.


Assuntos
Anemia Falciforme/sangue , Antidrepanocíticos/uso terapêutico , Hidroxiureia/uso terapêutico , Metabolômica , Ácidos/sangue , Síndrome Torácica Aguda/etiologia , Adolescente , Aminoácidos/sangue , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/farmacologia , Arteriopatias Oclusivas/etiologia , Biomarcadores , Butiratos/sangue , Criança , Cromatografia Líquida de Alta Pressão , Creatina/sangue , Creatinina/sangue , Feminino , Humanos , Hidroxiureia/farmacologia , Lisofosfolipídeos/sangue , Masculino , Espectrometria de Massas , Lipídeos de Membrana/sangue , Modelos Biológicos , Ressonância Magnética Nuclear Biomolecular , Esfingosina/análogos & derivados , Esfingosina/sangue
11.
Sci Rep ; 10(1): 18982, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33149225

RESUMO

Sickle cell anemia (SCA) is the most common inherited hemolytic anemia worldwide. Here, we performed an exploratory study to investigate the systemic oxidative stress in children and adolescents with SCA. Additionally, we evaluated the potential impact of hydroxyurea therapy on the status of oxidative stress in a case-control study from Brazil. To do so, a panel containing 9 oxidative stress markers was measured in plasma samples from a cohort of 47 SCA cases and 40 healthy children and adolescents. Among the SCA patients, 42.5% were undertaking hydroxyurea. Multidimensional analysis was employed to describe disease phenotypes. Our results demonstrated that SCA is associated with increased levels of oxidative stress markers, suggesting the existence of an unbalanced inflammatory response in peripheral blood. Subsequent analyses revealed that hydroxyurea therapy was associated with diminished oxidative imbalance in SCA patients. Our findings reinforce the idea that SCA is associated with a substantial dysregulation of oxidative responses which may be dampened by treatment with hydroxyurea. If validated by larger prospective studies, our observations argue that reduction of oxidative stress may be a main mechanism through which hydroxyurea therapy attenuates the tissue damage and can contribute to improved clinical outcomes in SCA.


Assuntos
Anemia Falciforme/tratamento farmacológico , Biomarcadores/sangue , Hidroxiureia/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Adolescente , Anemia Falciforme/sangue , Brasil , Estudos de Casos e Controles , Criança , Feminino , Humanos , Hidroxiureia/farmacologia , Masculino , Análise de Componente Principal , Estudos Prospectivos , Resultado do Tratamento
13.
Nat Commun ; 9(1): 2262, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891932

RESUMO

The ancient morphoregulatory hormone auxin dynamically realigns dedicated cellular processes that shape plant growth under prevailing environmental conditions. However, the nature of the stress-responsive signal altering auxin homeostasis remains elusive. Here we establish that the evolutionarily conserved plastidial retrograde signaling metabolite methylerythritol cyclodiphosphate (MEcPP) controls adaptive growth by dual transcriptional and post-translational regulatory inputs that modulate auxin levels and distribution patterns in response to stress. We demonstrate that in vivo accumulation or exogenous application of MEcPP alters the expression of two auxin reporters, DR5:GFP and DII-VENUS, and reduces the abundance of the auxin-efflux carrier PIN-FORMED1 (PIN1) at the plasma membrane. However, pharmacological intervention with clathrin-mediated endocytosis blocks the PIN1 reduction. This study provides insight into the interplay between these two indispensable signaling metabolites by establishing the mode of MEcPP action in altering auxin homeostasis, and as such, positioning plastidial function as the primary driver of adaptive growth.


Assuntos
Eritritol/análogos & derivados , Ácidos Indolacéticos/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Adaptação Fisiológica , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Clatrina/metabolismo , Endocitose , Eritritol/metabolismo , Homeostase , Luz , Proteínas de Membrana Transportadoras/metabolismo , Plantas Geneticamente Modificadas
14.
Mol Plant ; 10(11): 1400-1416, 2017 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-28965830

RESUMO

Plants have evolved tightly regulated signaling networks to respond and adapt to environmental perturbations, but the nature of the signaling hub(s) involved have remained an enigma. We have previously established that methylerythritol cyclodiphosphate (MEcPP), a precursor of plastidial isoprenoids and a stress-specific retrograde signaling metabolite, enables cellular readjustments for high-order adaptive functions. Here, we specifically show that MEcPP promotes two Brassicaceae-specific traits, namely endoplasmic reticulum (ER) body formation and induction of indole glucosinolate (IGs) metabolism selectively, via transcriptional regulation of key regulators NAI1 for ER body formation and MYB51/122 for IGs biosynthesis). The specificity of MEcPP is further confirmed by the lack of induction of wound-inducible ER body genes as well as IGs by other altered methylerythritol phosphate pathway enzymes. Genetic analyses revealed MEcPP-mediated COI1-dependent induction of these traits. Moreover, MEcPP signaling integrates the biosynthesis and hydrolysis of IGs through induction of nitrile-specifier protein1 and reduction of the suppressor, ESM1, and production of simple nitriles as the bioactive end product. The findings position the plastidial metabolite, MEcPP, as the initiation hub, transducing signals to adjust the activity of hard-wired gene circuitry to expand phytochemical diversity and alter the associated subcellular structure required for functionality of the secondary metabolites, thereby tailoring plant stress responses.


Assuntos
Glucosinolatos/metabolismo , Plastídeos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
15.
Plant J ; 91(1): 70-84, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28370892

RESUMO

To maintain homeostasis in the face of intrinsic and extrinsic insults, cells have evolved elaborate quality control networks to resolve damage at multiple levels. Interorganellar communication is a key requirement for this maintenance, however the underlying mechanisms of this communication have remained an enigma. Here we integrate the outcome of transcriptomic, proteomic, and metabolomics analyses of genotypes including ceh1, a mutant with constitutively elevated levels of both the stress-specific plastidial retrograde signaling metabolite methyl-erythritol cyclodiphosphate (MEcPP) and the defense hormone salicylic acid (SA), as well as the high MEcPP but SA deficient genotype ceh1/eds16, along with corresponding controls. Integration of multi-omic analyses enabled us to delineate the function of MEcPP from SA, and expose the compartmentalized role of this retrograde signaling metabolite in induction of distinct but interdependent signaling cascades instrumental in adaptive responses. Specifically, here we identify strata of MEcPP-sensitive stress-response cascades, among which we focus on selected pathways including organelle-specific regulation of jasmonate biosynthesis; simultaneous induction of synthesis and breakdown of SA; and MEcPP-mediated alteration of cellular redox status in particular glutathione redox balance. Collectively, these integrated multi-omic analyses provided a vehicle to gain an in-depth knowledge of genome-metabolism interactions, and to further probe the extent of these interactions and delineate their functional contributions. Through this approach we were able to pinpoint stress-mediated transcriptional and metabolic signatures and identify the downstream processes modulated by the independent or overlapping functions of MEcPP and SA in adaptive responses.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Glutationa/metabolismo , Metabolômica/métodos , Oxilipinas/metabolismo , Proteômica/métodos , Ácido Salicílico/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Transcriptoma/genética
16.
Annu Rev Plant Biol ; 68: 85-108, 2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-27813652

RESUMO

Interorganellar cooperation maintained via exquisitely controlled retrograde-signaling pathways is an evolutionary necessity for maintenance of cellular homeostasis. This signaling feature has therefore attracted much research attention aimed at improving understanding of the nature of these communication signals, how the signals are sensed, and ultimately the mechanism by which they integrate targeted processes that collectively culminate in organellar cooperativity. The answers to these questions will provide insight into how retrograde-signal-mediated regulatory mechanisms are recruited and which biological processes are targeted, and will advance our understanding of how organisms balance metabolic investments in growth against adaptation to environmental stress. This review summarizes the present understanding of the nature and the functional complexity of retrograde signals as integrators of interorganellar communication and orchestrators of plant development, and offers a perspective on the future of this critical and dynamic area of research.


Assuntos
Modelos Biológicos , Desenvolvimento Vegetal/fisiologia , Plantas/metabolismo , Cloroplastos/metabolismo , Retículo Endoplasmático/metabolismo , Mitocôndrias/metabolismo , Células Vegetais/metabolismo , Células Vegetais/ultraestrutura , Plantas/ultraestrutura , Transdução de Sinais , Estresse Fisiológico
17.
Proc Natl Acad Sci U S A ; 113(31): 8855-60, 2016 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-27432993

RESUMO

The general stress response (GSR) is an evolutionarily conserved rapid and transient transcriptional reprograming of genes central for transducing environmental signals into cellular responses, leading to metabolic and physiological readjustments to cope with prevailing conditions. Defining the regulatory components of the GSR will provide crucial insight into the design principles of early stress-response modules and their role in orchestrating master regulators of adaptive responses. Overaccumulation of methylerythritol cyclodiphosphate (MEcPP), a bifunctional chemical entity serving as both a precursor of isoprenoids produced by the plastidial methylerythritol phosphate (MEP) pathway and a stress-specific retrograde signal, in ceh1 (constitutively expressing hydroperoxide lyase1)-mutant plants leads to large-scale transcriptional alterations. Bioinformatic analyses of microarray data in ceh1 plants established the overrepresentation of a stress-responsive cis element and key GSR marker, the rapid stress response element (RSRE), in the promoters of robustly induced genes. ceh1 plants carrying an established 4×RSRE:Luciferase reporter for monitoring the GSR support constitutive activation of the response in this mutant background. Genetics and pharmacological approaches confirmed the specificity of MEcPP in RSRE induction via the transcription factor CALMODULIN-BINDING TRANSCRIPTION ACTIVATOR 3 (CAMTA3), in a calcium-dependent manner. Moreover, CAMTA3-dependent activation of IRE1a (inositol-requiring protein-1) and bZIP60 (basic leucine zipper 60), two RSRE containing unfolded protein-response genes, bridges MEcPP-mediated GSR induction to the potentiation of protein-folding homeostasis in the endoplasmic reticulum. These findings introduce the notion of transcriptional regulation by a key plastidial retrograde signaling metabolite that induces nuclear GSR, thereby offering a window into the role of interorgannellar communication in shaping cellular adaptive responses.


Assuntos
Proteínas de Arabidopsis/metabolismo , Eritritol/análogos & derivados , Regulação da Expressão Gênica de Plantas , Plastídeos/metabolismo , Estresse Fisiológico , Fatores de Transcrição/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Cálcio/metabolismo , Enzimas/genética , Enzimas/metabolismo , Eritritol/metabolismo , Eritritol/farmacologia , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Mutação , Reguladores de Crescimento de Plantas/metabolismo , Elementos de Resposta/genética , Fosfatos Açúcares/metabolismo , Fatores de Transcrição/genética , Resposta a Proteínas não Dobradas/genética
18.
J Exp Bot ; 67(5): 1557-66, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26733689

RESUMO

The exquisite harmony between hormones and their corresponding signaling pathways is central to prioritizing plant responses to simultaneous and/or successive environmental trepidations. The crosstalk between jasmonic acid (JA) and salicylic acid (SA) is an established effective mechanism that optimizes and tailors plant adaptive responses. However, the underlying regulatory modules of this crosstalk are largely unknown. Global transcriptomic analyses of mutant plants (ceh1) with elevated levels of the stress-induced plastidial retrograde signaling metabolite 2-C-methyl-D-erythritol cyclopyrophosphate (MEcPP) revealed robustly induced JA marker genes, expected to be suppressed by the presence of constitutively high SA levels in the mutant background. Analyses of a range of genotypes with varying SA and MEcPP levels established the selective role of MEcPP-mediated signal(s) in induction of JA-responsive genes in the presence of elevated SA. Metabolic profiling revealed the presence of high levels of the JA precursor 12-oxo-phytodienoic acid (OPDA), but near wild type levels of JA in the ceh1 mutant plants. Analyses of coronatine-insensitive 1 (coi1)/ceh1 double mutant plants confirmed that the MEcPP-mediated induction is JA receptor COI1 dependent, potentially through elevated OPDA. These findings identify MEcPP as a previously unrecognized central regulatory module that induces JA-responsive genes in the presence of high SA, thereby staging a multifaceted plant response within the environmental context.


Assuntos
Arabidopsis/metabolismo , Ciclopentanos/metabolismo , Eritritol/análogos & derivados , Oxilipinas/metabolismo , Plastídeos/metabolismo , Ácido Salicílico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Eritritol/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Modelos Biológicos , Mutação/genética , Plastídeos/efeitos dos fármacos
19.
Plant Signal Behav ; 10(9): e1055434, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26237162

RESUMO

Pectin acetylation influences the gelling ability of this important plant polysaccharide for the food industry. Plant apoplastic pectinacetylesterases (PAEs) play a key role in regulating the degree of pectin acetylation and modifying their expression thus represents one way to engineer plant polysaccharides for food applications. Identifying the major active enzymes within the PAE gene family will aid in our understanding of this biological phenomena as well as provide the tools for direct trait manipulation. Using comparative genomics we propose that there is a minimal set of 4 distinct PAEs in plants. Possible functional diversification of the PAE family in the grasses is also explored with the identification of 3 groups of PAE genes specific to grasses.


Assuntos
Esterases/metabolismo , Genômica , Acetatos/metabolismo , Arabidopsis/enzimologia , Pectinas/metabolismo , Filogenia , Especificidade da Espécie
20.
Plant Physiol ; 167(3): 711-24, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25583925

RESUMO

Differentiation of the maternally derived seed coat epidermal cells into mucilage secretory cells is a common adaptation in angiosperms. Recent studies identified cellulose as an important component of seed mucilage in various species. Cellulose is deposited as a set of rays that radiate from the seed upon mucilage extrusion, serving to anchor the pectic component of seed mucilage to the seed surface. Using transcriptome data encompassing the course of seed development, we identified COBRA-LIKE2 (COBL2), a member of the glycosylphosphatidylinositol-anchored COBRA-LIKE gene family in Arabidopsis (Arabidopsis thaliana), as coexpressed with other genes involved in cellulose deposition in mucilage secretory cells. Disruption of the COBL2 gene results in substantial reduction in the rays of cellulose present in seed mucilage, along with an increased solubility of the pectic component of the mucilage. Light birefringence demonstrates a substantial decrease in crystalline cellulose deposition into the cellulosic rays of the cobl2 mutants. Moreover, crystalline cellulose deposition into the radial cell walls and the columella appears substantially compromised, as demonstrated by scanning electron microscopy and in situ quantification of light birefringence. Overall, the cobl2 mutants display about 40% reduction in whole-seed crystalline cellulose content compared with the wild type. These data establish that COBL2 plays a role in the deposition of crystalline cellulose into various secondary cell wall structures during seed coat epidermal cell differentiation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/citologia , Arabidopsis/metabolismo , Celulose/metabolismo , Glicosilfosfatidilinositóis/metabolismo , Proteínas de Membrana/metabolismo , Sementes/citologia , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Birrefringência , Cátions , Diferenciação Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Quelantes/farmacologia , Cristalização , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Membrana/genética , Mutação , Especificidade de Órgãos/efeitos dos fármacos , Pectinas/metabolismo , Epiderme Vegetal/citologia , Epiderme Vegetal/efeitos dos fármacos , Mucilagem Vegetal/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/ultraestrutura , Solubilidade
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