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1.
Nat Commun ; 14(1): 2692, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37164975

RESUMO

Mapping tumor metabolic remodeling and their spatial crosstalk with surrounding non-tumor cells can fundamentally improve our understanding of tumor biology, facilitates the designing of advanced therapeutic strategies. Here, we present an integration of mass spectrometry imaging-based spatial metabolomics and lipidomics with microarray-based spatial transcriptomics to hierarchically visualize the intratumor metabolic heterogeneity and cell metabolic interactions in same gastric cancer sample. Tumor-associated metabolic reprogramming is imaged at metabolic-transcriptional levels, and maker metabolites, lipids, genes are connected in metabolic pathways and colocalized in the heterogeneous cancer tissues. Integrated data from spatial multi-omics approaches coherently identify cell types and distributions within the complex tumor microenvironment, and an immune cell-dominated "tumor-normal interface" region where tumor cells contact adjacent tissues are characterized with distinct transcriptional signatures and significant immunometabolic alterations. Our approach for mapping tissue molecular architecture provides highly integrated picture of intratumor heterogeneity, and transform the understanding of cancer metabolism at systemic level.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Multiômica , Metabolômica/métodos , Espectrometria de Massas , Perfilação da Expressão Gênica , Microambiente Tumoral
2.
Int J Mol Sci ; 20(24)2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31817230

RESUMO

Ganoderma lucidum is widely recognized as a medicinal basidiomycete. It was previously reported that the plant hormone methyl jasmonate (MeJA) could induce the biosynthesis of ganoderic acids (GAs), which are the main active ingredients of G. lucidum. However, the regulatory mechanism is still unclear. In this study, integrated proteomics and metabolomics were employed on G. lucidum to globally identify differences in proteins and metabolites under MeJA treatment for 15 min (M15) and 24 h (M24). Our study successfully identified 209 differential abundance proteins (DAPs) in M15 and 202 DAPs in M24. We also identified 154 metabolites by GC-MS and 70 metabolites by LC-MS in M24 that are involved in several metabolic pathways. With an in-depth analysis, we found some DAPs and metabolites that are involved in the oxidoreduction process, secondary metabolism, energy metabolism, transcriptional and translational regulation, and protein synthesis. In particular, our results reveal that MeJA treatment leads to metabolic rearrangement that inhibited the normal glucose metabolism, energy supply, and protein synthesis of cells but promoted secondary metabolites, including GAs. In conclusion, our proteomics and metabolomics data further confirm the promoting effect of MeJA on the biosynthesis of GAs in G. lucidum and will provide a valuable resource for further investigation of the molecular mechanisms of MeJA signal response and GA biosynthesis in G. lucidum and other related species.


Assuntos
Acetatos/farmacologia , Ciclopentanos/farmacologia , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Oxilipinas/farmacologia , Proteoma/análise , Proteômica/métodos , Reishi/metabolismo , Triterpenos/metabolismo , Cromatografia Líquida de Alta Pressão , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas
3.
Proteomics ; 11(21): 4122-38, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21818852

RESUMO

We used proteomic analysis to determine the response of rice plant seedlings to drought-induced stress. The expression of 71 protein spots was significantly altered, and 60 spots were successfully identified. The greatest down-regulated protein functional category was translation. Up-regulated proteins were mainly related to protein folding and assembly. Additionally, many proteins involved in metabolism (e.g. carbohydrate metabolism) also showed differences in expression. cDNA microarray and GC-MS analysis showed 4756 differentially expressed mRNAs and 37 differentially expressed metabolites. Once these data were integrated with the proteomic analysis, we were able to elucidate the metabolic pathways affected by drought-induced stress. These results suggest that increased energy consumption from storage substances occurred during drought. In addition, increased expression of the enzymes involved in anabolic pathways corresponded with an increase in the content of six amino acids. We speculated that energy conversion from carbohydrates and/or fatty acids to amino acids was increased. Analysis of basic metabolism networks allowed us to understand how rice plants adjust to drought conditions.


Assuntos
Metabolismo Energético , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteômica , Plântula/metabolismo , Secas , Regulação da Expressão Gênica de Plantas , Redes e Vias Metabólicas , Análise de Sequência com Séries de Oligonucleotídeos , Oryza/genética , Proteínas de Plantas/genética , Plântula/genética
4.
J Integr Plant Biol ; 52(11): 981-95, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20977656

RESUMO

Following the idea of partial root-zone drying (PRD) in crop cultivation, the morphological and physiological responses to partial root osmotic stress (PROS) and whole root osmotic stress (WROS) were investigated in rice. WROS caused stress symptoms like leaf rolling and membrane leakage. PROS stimulated stress signals, but did not cause severe leaf damage. By proteomic analysis, a total of 58 proteins showed differential expression after one or both treatments, and functional classification of these proteins suggests that stress signals regulate photosynthesis, carbohydrate and energy metabolism. Two other proteins (anthranilate synthase and submergence-induced nickel-binding protein) were upregulated only in the PROS plants, indicating their important roles in stress resistance. Additionally, more enzymes were involved in stress defense, redox homeostasis, lignin and ethylene synthesis in WROS leaves, suggesting a more comprehensive regulatory mechanism induced by osmotic stress. This study provides new insights into the complex molecular networks within plant leaves involved in the adaptation to osmotic stress and stress signals.


Assuntos
Oryza/metabolismo , Osmose/fisiologia , Folhas de Planta/metabolismo , Proteômica/métodos , Transdução de Sinais , Estresse Fisiológico , Sequência de Aminoácidos , Eletroforese em Gel Bidimensional , Espectrometria de Massas , Dados de Sequência Molecular , Oryza/anatomia & histologia , Proteínas de Plantas/química , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Raízes de Plantas/fisiologia
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