scholarly journals Synthesis and Evaluation of a Stable Isostere of Malonyllysine

2020 ◽  
Author(s):  
Sarah E. Bergholtz ◽  
Yihang Jing ◽  
Rhushikesh A. Kulkarni ◽  
Thomas T. Zengeya ◽  
Jordan L. Meier
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Energy Metabolism ◽  
Posttranslational Modification ◽  
Negative Charge ◽  
Tool Development ◽  
Lysine Modification ◽  
Functional Analyses ◽  
Chemical Strategy ◽  
Thermal Decarboxylation

AbstractLysine malonylation is a recently characterized posttranslational modification involved in the regulation of energy metabolism and gene expression. Two unique features of this posttranslational modification are its negative charge and potential susceptibility to decarboxylation, both of which pose possible challenges to its study. As a step towards addressing these challenges, here we report the synthesis and evaluation of a stable isostere of malonyllysine. First, we find that synthetic substitution of the malonyl group with a tetrazole isostere results in amino acids resistant to thermal decarboxylation. Next, we demonstrate that protected variants of this amino acid are readily incorporated into peptides. Finally, we show that tetrazole isosteres of malonyllysine can be recognized by anti-malonyllysine antibodies, validating their ability to mimic features of the endogenous lysine modification. Overall, this study establishes a new chemical strategy for stably mimicking a metabolite-derived posttranslational modification, providing a foothold for tool development and functional analyses.

scholarly journals The Effects of Radix Astragali Water Abstract on Energy Metabolism in Rat Yang-Deficiency Cold Syndrome Model through PPAR Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-19 ◽  
Author(s):  
Wanchen Yu ◽  
Haijun Zhao ◽  
Xin Zong ◽  
Xuming Ji ◽  
Xiaochun Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Energy Metabolism ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metabolic Process ◽  
Metabolic Function ◽  
Radix Astragali ◽  
Ppar Signaling

Radix Astragali (RA) herb with warm property and significant “tonifying qi” effects is indicated for the syndrome of internal cold due to Yang deficiency. The purpose of this research was to explore effects of Radix Astragali (RA) through PPAR signaling pathway on gene expression profiles related to energy metabolism in rats with the Yang-deficiency cold (YDC) syndrome, for identifying the pathological mechanism of Yang-deficiency cold (YDC) syndrome and the effects mechanism of RA. The results indicated that RA could significantly increase body weight (BM), cold and heat tendency (CT), overall temperature (OT), rectum temperature (RT), toe temperature (TT), energy intake (EI), and V(O2)/V(CO2) ratio (which indicates basal metabolism, BM) (P<0.05), enhancing the depressed metabolic function in YDC syndrome model rat. Our data also indicated differentially expressed genes (DEGs) related to energy metabolism involving lipids, carbohydrates, and amino acids metabolic process; the expression of CPT-1 and FABP4 (ap2) was improved; PPAR, Glycolysis, Wnt, cAMP, MAPK, AMPK, and fatty acid degradation signaling pathway may be related to energy metabolism. However, the Chinese herbal medicine RA plays a certain role in promoting the metabolism of substances and energy in rats by its warming and beneficial effect. Our results suggest that the mechanism underlying the function of RA may take effect through the regulation of PPAR signaling pathway and related gene expression. Lipids, carbohydrates, and amino acids metabolic process may be affected to adjust the reduced metabolic function in the model animals. In general, results indicate that RA could promote energy metabolism in rats with the YDC syndrome via PPAR signaling pathway regulating the expression of CPT-1 and FABP4 (ap2), which reflected the warm and qi tonifying properties of RA.

Long term dietary intake of aromatic amino acids are associated with leptin gene expression in adipose tissues of non-diabetic adults

2018 ◽  
Author(s):  
Golaleh Asghari ◽  
Emad Yuzbashian ◽  
Maryam Zarkesh ◽  
Parvin Mirmiran ◽  
Mehdi Hedayati ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Dietary Intake ◽  
Aromatic Amino Acids ◽  
Adipose Tissues

scholarly journals Identification of glycolysis related pathways in pancreatic adenocarcinoma and liver hepatocellular carcinoma based on TCGA and GEO datasets

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ji Li ◽  
Chen Zhu ◽  
Peipei Yue ◽  
Tianyu Zheng ◽  
Yan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Energy Metabolism ◽  
Pancreatic Adenocarcinoma ◽  
Digestive System ◽  
Prognostic Significance ◽  
R Package ◽  
The Cancer Genome Atlas ◽  
System Structure ◽  
Liver Hepatocellular Carcinoma

Abstract Background Abnormal energy metabolism is one of the characteristics of tumor cells, and it is also a research hotspot in recent years. Due to the complexity of digestive system structure, the frequency of tumor is relatively high. We aim to clarify the prognostic significance of energy metabolism in digestive system tumors and the underlying mechanisms. Methods Gene set variance analysis (GSVA) R package was used to establish the metabolic score, and the score was used to represent the metabolic level. The relationship between the metabolism and prognosis of digestive system tumors was explored using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Volcano plots and gene ontology (GO) analyze were used to show different genes and different functions enriched between different glycolysis levels, and GSEA was used to analyze the pathway enrichment. Nomogram was constructed by R package based on gene characteristics and clinical parameters. qPCR and Western Blot were applied to analyze gene expression. All statistical analyses were conducted using SPSS, GraphPad Prism 7, and R software. All validated experiments were performed three times independently. Results High glycolysis metabolism score was significantly associated with poor prognosis in pancreatic adenocarcinoma (PAAD) and liver hepatocellular carcinoma (LIHC). The STAT3 (signal transducer and activator of transcription 3) and YAP1 (Yes1-associated transcriptional regulator) pathways were the most critical signaling pathways in glycolysis modulation in PAAD and LIHC, respectively. Interestingly, elevated glycolysis levels could also enhance STAT3 and YAP1 activity in PAAD and LIHC cells, respectively, forming a positive feedback loop. Conclusions Our results may provide new insights into the indispensable role of glycolysis metabolism in digestive system tumors and guide the direction of future metabolism–signaling target combined therapy.

scholarly journals PSIV-6 Effect of a Phytogenic Water Additive on Growth Performance, Blood Metabolites and Gene Expression of Amino Acids Transporters in Nursery Pigs Fed with Low Protein Diets

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 281-282
Author(s):  
Cedrick N Shili ◽  
Mohammad Habibi ◽  
Julia Sutton ◽  
Jessie Barnes ◽  
Jacob Burchkonda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Growth Performance ◽  
Mrna Abundance ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Blood Calcium ◽  
Low Protein ◽  
Protein Diets ◽  
Standard Protein

Abstract Moderately low protein (MLP) diets can help decrease nutrient excretion from the swine production. However, MLP diets negatively impact growth performance. We hypothesized that supplementing MLP diets with phytogenics may reduce the negative effects of these diets on growth. The objective of this study was to investigate the effect of a phytogenic water additive (PWA; Herbanimal®) on growth performance, blood metabolite and gene expression of amino acids transporters in pigs fed with MLP diets. Forty-eight weaned barrows were allotted to six dietary treatments (n = 8) for 4 weeks: &gt;CON-NS: standard protein diet-no PWA; CON-LS: standard protein diet-low PWA dose (4 ml/L); CON-HS: standard protein diet-high PWA dose (8 ml/L); LP-NS: low protein diet-no PWA; LP-LS: low protein diet-low PWA dose (4 ml/L); LP-HS: low protein diet- high PWA dose (8 ml/L). Feed intake and body weight were recorded daily and weekly, respectively. At week 4, blood and tissue samples were collected and analyzed for metabolites using a chemistry analyzer and amino acid transporters using qPCR, respectively. The data were analyzed by univariate GLM (SPSS®) and the means were separated using paired Student’s t-test corrected by Benjamini-Hochberg. Pigs fed CON-HS improved the average daily gain and serum calcium and phosphorus concentrations compared to CON-NS. Pigs fed LP-LS had higher serum phosphorus and blood urea nitrogen compared to the pigs fed with LP-NS. The mRNA abundance of SLC7A11 in the jejunum was lower in CON-LS and CON-HS compared to CON-NS. Additionally, mRNA abundance of SLC6A19 in the jejunum of pigs fed with LP-LS was higher compared to LP-NS and lower in CON-HS relative to pigs fed with CON-LS. In conclusion, PWA improved the growth performance of pigs fed standard protein diets but not low protein diets. Further, the PWA improved the concentrations of blood calcium and phosphorous in pigs fed MLP diets. Funding: Agrivida and Animal Health and Production and Animal Products: Improved Nutritional Performance, Growth, and Lactation of Animals from the USDA-NIFA.

scholarly journals Proteomic and Transcriptomic Analyses Provide Novel Insights into the Crucial Roles of Host-Induced Carbohydrate Metabolism Enzymes in Xanthomonas oryzae pv. oryzae Virulence and Rice-Xoo Interaction

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guichun Wu ◽  
Yuqiang Zhang ◽  
Bo Wang ◽  
Kaihuai Li ◽  
Yuanlai Lou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Amino Acids ◽  
Secondary Metabolites ◽  
Carbohydrate Metabolism ◽  
Virulence Factors ◽  
Global Gene Expression ◽  
Xanthomonas Oryzae ◽  
Oxidation Reduction ◽  
Phenylpropanoid Biosynthesis

Abstract Background Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial leaf blight, a devastating rice disease. The Xoo-rice interaction, wherein wide ranging host- and pathogen-derived proteins and genes wage molecular arms race, is a research hotspot. Hence, the identification of novel rice-induced Xoo virulence factors and characterization of their roles affecting rice global gene expression profiles will provide an integrated and better understanding of Xoo-rice interactions from the molecular perspective. Results Using comparative proteomics and an in vitro interaction system, we revealed that 5 protein spots from Xoo exhibited significantly different expression patterns (|fold change| > 1.5) at 3, 6, 12 h after susceptible rice leaf extract (RLX) treatment. MALDI-TOF MS analysis and pathogenicity tests showed that 4 host-induced proteins, including phosphohexose mutase, inositol monophosphatase, arginase and septum site-determining protein, affected Xoo virulence. Among them, mutants of two host-induced carbohydrate metabolism enzyme-encoding genes, ΔxanA and Δimp, elicited enhanced defense responses and nearly abolished Xoo virulence in rice. To decipher rice differentially expressed genes (DEGs) associated with xanA and imp, transcriptomic responses of ΔxanA-treated and Δimp-treated susceptible rice were compared to those in rice treated with PXO99A at 1 and 3 dpi. A total of 1521 and 227 DEGs were identified for PXO99A vs Δimp at 1 and 3 dpi, while for PXO99A vs ΔxanA, there were 131 and 106 DEGs, respectively. GO, KEGG and MapMan analyses revealed that the DEGs for PXO99A vs Δimp were mainly involved in photosynthesis, signal transduction, transcription, oxidation-reduction, hydrogen peroxide catabolism, ion transport, phenylpropanoid biosynthesis and metabolism of carbohydrates, lipids, amino acids, secondary metabolites, hormones, and nucleotides, while the DEGs from PXO99A vs ΔxanA were predominantly associated with photosynthesis, signal transduction, oxidation-reduction, phenylpropanoid biosynthesis, cytochrome P450 and metabolism of carbohydrates, lipids, amino acids, secondary metabolites and hormones. Although most pathways were associated with both the Δimp and ΔxanA treatments, the underlying genes were not the same. Conclusion Our study identified two novel host-induced virulence factors XanA and Imp in Xoo, and revealed their roles in global gene expression in susceptible rice. These results provide valuable insights into the molecular mechanisms of pathogen infection strategies and plant immunity.

scholarly journals Selection of reference genes for gene expression analysis in Liriodendron hybrids’ somatic embryogenesis and germinative tissues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tingting Li ◽  
Weigao Yuan ◽  
Shuai Qiu ◽  
Jisen Shi
Keyword(s):  
Gene Expression ◽  
Somatic Embryogenesis ◽  
Reference Genes ◽  
Gene Selection ◽  
Elongation Factor ◽  
Reverse Transcription Pcr ◽  
Expression Of Genes ◽  
Suitable Reference ◽  
Functional Analyses ◽  
Elongation Factor 1

AbstractThe differential expression of genes is crucial for plant somatic embryogenesis (SE), and the accurate quantification of gene expression levels relies on choosing appropriate reference genes. To select the most suitable reference genes for SE studies, 10 commonly used reference genes were examined in synchronized somatic embryogenic and subsequent germinative cultures of Liriodendron hybrids by using quantitative real-time reverse transcription PCR. Four popular normalization algorithms: geNorm, NormFinder, Bestkeeper and Delta-Ct were used to select and validate the suitable reference genes. The results showed that elongation factor 1-gamma, histone H1 linker protein, glyceraldehyde-3-phosphate dehydrogenase and α-tubulin were suitable for SE tissues, while elongation factor 1-gamma and actin were best for the germinative organ tissues. Our work will benefit future studies of gene expression and functional analyses of SE in Liriodendron hybrids. It is also serves as a guide of reference gene selection in early embryonic gene expression analyses for other woody plant species.

scholarly journals Expression of DDX11 and DNM1L at the 12p11 Locus Modulates Systemic Lupus Erythematosus Susceptibility

2021 ◽  
Vol 22 (14) ◽  
pp. 7624
Author(s):  
Mohammad Saeed ◽  
Alejandro Ibáñez-Costa ◽  
Alejandra María Patiño-Trives ◽  
Laura Muñoz-Barrera ◽  
Eduardo Collantes Estévez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lupus Erythematosus ◽  
Genome Stability ◽  
Meta Analysis ◽  
Susceptibility Gene ◽  
Significant Snps ◽  
Differentially Expressed ◽  
Systemic Lupus Erythematosus Susceptibility ◽  
Functional Pathways ◽  
Functional Analyses

Objectives: This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes. Methods: Four hundred and ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Confirmatory qPCR on SLE monocytes was performed. The entire 12p11 locus was investigated for genetic association using two additional GWAS. Expression of 150 genes at this locus was assessed. Based on this significance, qPCRs for DNM1L and KRAS were performed. Results: Fifty genes were differentially expressed in at least two SLE GEO-datasets, with all probes directionally aligned. DDX11, an RNA helicase involved in genome stability, was downregulated in both GEO and Cordoba datasets. The most significant SNP, rs3741869 in OASIS locus 12p11.21, containing DDX11, was a cis-eQTL regulating DDX11 expression. DDX11 was found repressed. The entire 12p11 locus showed three association peaks. Gene expression in GEO datasets identified DNM1L and KRAS, besides DDX11. Confirmatory qPCR validated DNM1L as an SLE susceptibility gene. DDX11, DNM1L and KRAS interact with each other and multiple known SLE genes including STAT1/STAT4 and major components of IFN-dependent gene expression, and are responsible for signal transduction of cytokines, hormones, and growth-factors, deregulation of which is involved in SLE-development. Conclusion: A genomic convergence approach with OASIS analysis of multiple GWAS and expression datasets identified DDX11 and DNM1L as novel SLE-genes, the expression of which is altered in monocytes from SLE patients. This study lays the foundation for understanding the pathogenic involvement of DDX11 and DNM1L in SLE by identifying them using a systems-biology approach, while the 12p11 locus harboring these genes was previously missed by four independent GWAS.

scholarly journals Regulation of rat magnocellular neurosecretory system by D-aspartate: evidence for biological role(s) of a naturally occurring free D-amino acid in mammals

2000 ◽  
Vol 167 (2) ◽  
pp. 247-252 ◽  
Author(s):  
H Wang ◽  
H Wolosker ◽  
J Pevsner ◽  
SH Snyder ◽  
DJ Selkoe
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Amino Acid ◽  
Physiological Function ◽  
Neurosecretory System ◽  
Milk Ejection ◽  
Magnocellular Neurons ◽  
Rat Hypothalamus ◽  
Naturally Occurring

Little evidence is available for the physiological function of D-amino acids in species other than bacteria. Here we demonstrate that naturally occurring freed -aspartate (D-Asp) is present in all magnocellular neurons of rat hypothalamus. The levels of this naturally occurring D-amino acid were elevated during lactation and returned to normal thereafter in the magnocellular neurosecretory system, which produces oxytocin, a hormone responsible for milk ejection during lactation. Intraperitoneal injections of D-Asp reproducibly increased oxytocin gene expression and decreased the concentration of circulating oxytocin in vivo. Similar changes were observed in the vasopressin system. These results provide evidence for the role(s) of naturally occurring free D-Asp in mammalian physiology. The findings argue against the conventional concept that only L-stereoisomers of amino acids are functional in higher species.

Sign in / Sign up

Export Citation Format

Share Document