scholarly journals The analysis of glutamate and glutamine frequencies in human proteins as marker of tissue oxygenation

2019 ◽  
Vol 6 (4) ◽  
pp. 181891 ◽  
Author(s):  
Annamaria Vernone ◽  
Chiara Ricca ◽  
Daniela Merlo ◽  
Gianpiero Pescarmona ◽  
Francesca Silvagno

In this study, we investigated whether the relative abundance of glutamate and glutamine in human proteins reflects the availability of these amino acids (AAs) dictated by the cellular context. In particular, because hypoxia increases the conversion of glutamate to glutamine, we hypothesized that the ratio glutamate/glutamine could be related to tissue oxygenation. By histological, biochemical and genetic evaluation, we identified proteins expressed selectively by distinct cellular populations that are exposed in the same tissue to high or low oxygenation, or proteins codified by different chromosomal loci. Our biochemical assessment was implemented by software tools that calculated the absolute and the relative frequencies of all AAs contained in the proteins. Moreover, an agglomerative hierarchical cluster analysis was performed. In the skin model that has a strictly local metabolism, we demonstrated that the ratio glutamate/glutamine of the selected proteins was directly proportional to oxygenation. Accordingly, the proteins codified by the epidermal differentiation complex in the region 1q21.3 and by the lipase clustering region 10q23.31 showed a significantly lower ratio glutamate/glutamine compared with the nearby regions of the same chromosome. Overall, our results demonstrate that the estimation of glutamate/glutamine ratio can give information on tissue oxygenation and could be exploited as marker of hypoxia, a condition common to several pathologies.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mary Elizabeth Mathyer ◽  
Erin A. Brettmann ◽  
Alina D. Schmidt ◽  
Zane A. Goodwin ◽  
Inez Y. Oh ◽  
...  

AbstractThe genetic modules that contribute to human evolution are poorly understood. Here we investigate positive selection in the Epidermal Differentiation Complex locus for skin barrier adaptation in diverse HapMap human populations (CEU, JPT/CHB, and YRI). Using Composite of Multiple Signals and iSAFE, we identify selective sweeps for LCE1A-SMCP and involucrin (IVL) haplotypes associated with human migration out-of-Africa, reaching near fixation in European populations. CEU-IVL is associated with increased IVL expression and a known epidermis-specific enhancer. CRISPR/Cas9 deletion of the orthologous mouse enhancer in vivo reveals a functional requirement for the enhancer to regulate Ivl expression in cis. Reporter assays confirm increased regulatory and additive enhancer effects of CEU-specific polymorphisms identified at predicted IRF1 and NFIC binding sites in the IVL enhancer (rs4845327) and its promoter (rs1854779). Together, our results identify a selective sweep for a cis regulatory module for CEU-IVL, highlighting human skin barrier evolution for increased IVL expression out-of-Africa.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Pablo Mier ◽  
Miguel A. Andrade-Navarro

Abstract According to the amino acid composition of natural proteins, it could be expected that all possible sequences of three or four amino acids will occur at least once in large protein datasets purely by chance. However, in some species or cellular context, specific short amino acid motifs are missing due to unknown reasons. We describe these as Avoided Motifs, short amino acid combinations missing from biological sequences. Here we identify 209 human and 154 bacterial Avoided Motifs of length four amino acids, and discuss their possible functionality according to their presence in other species. Furthermore, we determine two Avoided Motifs of length three amino acids in human proteins specifically located in the cytoplasm, and two more in secreted proteins. Our results support the hypothesis that the characterization of Avoided Motifs in particular contexts can provide us with information about functional motifs, pointing to a new approach in the use of molecular sequences for the discovery of protein function.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
M. Mancini ◽  
A. Cappello ◽  
R. Pecorari ◽  
A. M. Lena ◽  
M. Montanaro ◽  
...  

AbstractWhile non-melanoma skin cancers (NMSCs) are the most common tumours in humans, only the sub-type cutaneous squamous cell carcinoma (cSCC), might become metastatic with high lethality. We have recently identified a regulatory pathway involving the lncRNA transcript uc.291 in controlling the expression of epidermal differentiation complex genes via the interaction with ACTL6A, a component of the chromatin remodelling complex SWI/SNF. Since transcribed ultra-conserved regions (T-UCRs) are expressed in normal tissues and are deregulated in tumorigenesis, here we hypothesize a potential role for dysregulation of this axis in cSCC, accounting for the de-differentiation process observed in aggressive poorly differentiated cutaneous carcinomas. We therefore analysed their expression patterns in human tumour biopsies at mRNA and protein levels. The results suggest that by altering chromatin accessibility of the epidermal differentiation complex genes, down-regulation of uc.291 and BRG1 expression contribute to the de-differentiation process seen in keratinocyte malignancy. This provides future direction for the identification of clinical biomarkers in cutaneous SCC. Analysis of publicly available data sets indicates that the above may also be a general feature for SCCs of different origins.


2014 ◽  
Vol 134 (9) ◽  
pp. 2371-2380 ◽  
Author(s):  
Inez Y. Oh ◽  
Danielle M. Albea ◽  
Zane A. Goodwin ◽  
Ashley M. Quiggle ◽  
Breeana P. Baker ◽  
...  

Genomics ◽  
1996 ◽  
Vol 37 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Ingo Marenholz ◽  
Armin Volz ◽  
Andreas Ziegler ◽  
Angela Davies ◽  
Ioannis Ragoussis ◽  
...  

Foods ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1425
Author(s):  
Jonas Yde Junge ◽  
Anne Sjoerup Bertelsen ◽  
Line Ahm Mielby ◽  
Yan Zeng ◽  
Yuan-Xia Sun ◽  
...  

Tastes interact in almost every consumed food or beverage, yet many aspects of interactions, such as sweet-sour interactions, are not well understood. This study investigated the interaction between sweetness from sucrose and sourness from citric and tartaric acid, respectively. A cross-cultural consumer study was conducted in China (n = 120) and Denmark (n = 139), respectively. Participants evaluated six aqueous samples with no addition (control), sucrose, citric acid, tartaric acid, or a mixture of sucrose and citric acid or sucrose and tartaric acid. No significant difference was found between citric acid and tartaric acid in the suppression of sweetness intensity ratings of sucrose. Further, sucrose suppressed sourness intensity ratings of citric acid and tartaric acid similarly. Culture did not impact the suppression of sweetness intensity ratings of citric or tartaric acid, whereas it did influence sourness intensity ratings. While the Danish consumers showed similar suppression of sourness by both acids, the Chinese consumers were more susceptible towards the sourness suppression caused by sucrose in the tartaric acid-sucrose mixture compared to the citric acid-sucrose mixture. Agglomerative hierarchical cluster analysis revealed clusters of consumers with significant differences in sweetness intensity ratings and sourness intensity ratings. These results indicate that individual differences in taste perception might affect perception of sweet-sour taste interactions, at least in aqueous solutions.


Genomics ◽  
2004 ◽  
Vol 83 (6) ◽  
pp. 1151-1163 ◽  
Author(s):  
Punam Mathur ◽  
Beth Murray ◽  
Thomas Crowell ◽  
Humphrey Gardner ◽  
Normand Allaire ◽  
...  

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1130
Author(s):  
Anna Połeć ◽  
Alexander D. Rowe ◽  
Pernille Blicher ◽  
Rajikala Suganthan ◽  
Magnar Bjørås ◽  
...  

The promyelocytic leukemia (PML) protein is an essential component of nuclear compartments called PML bodies. This protein participates in several cellular processes, including growth control, senescence, apoptosis, and differentiation. Previous studies have suggested that PML regulates gene expression at a subset of loci through a function in chromatin remodeling. Here we have studied global gene expression patterns in mouse embryonic skin derived from Pml depleted and wild type mouse embryos. Differential gene expression analysis at different developmental stages revealed a key role of PML in regulating genes involved in epidermal stratification. In particular, we observed dysregulation of the late cornified envelope gene cluster, which is a sub-region of the epidermal differentiation complex. In agreement with these data, PML body numbers are elevated in basal keratinocytes during embryogenesis, and we observed reduced epidermal thickness and defective hair follicle development in PML depleted mouse embryos.


2019 ◽  
Vol 20 (4) ◽  
pp. 914 ◽  
Author(s):  
Barbara Sobiak ◽  
Wiesława Leśniak

Epidermal differentiation is a complex process and its regulation may involve epigenetic factors. Analysis of DNA methylation in 20 selected regions within the epidermal differentiation complex (EDC) gene cluster by targeted next-generation sequencing (NGS) detected no or only minor changes in methylation, mostly slight demethylation, occurring during the course of keratinocyte differentiation. However, a single CpG pair within the exon of the PGLYRP3 gene underwent a pronounced demethylation concomitant with an increase in PGLYRP3 expression. We have employed a DNA-affinity precipitation assay (DAPA) and mass spectrometry to examine changes in the composition of proteins that bind to DNA containing either methylated or unmethylated CpG. We found that the unmethylated probe attracted mostly RNA binding proteins, including splicing factors, which suggests that demethylation of this particular CpG may facilitate PGLYRP3 transcription and/or pre-mRNA splicing.


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