Saliva panel of protein candidates: A comprehensive study for assessing high altitude acclimatization

Jain, Shikha; Paul, Subhojit; Meena, Rajesh Kumar; Gangwar, Anamika; Panjwani, Usha; Ahmad, Yasmin; Bhargava, Kalpana

doi:10.1016/j.niox.2019.11.007

Cited by 8 publications

(3 citation statements)

References 55 publications

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“…By comparing with sea level saliva proteome, the authors identified a higher abundance of apoptosis-inducing factor-2 (AIFM2), cystatin S (CST4), cystatin SN (CST1), and carbonic anhydrase 6 (CA6) proteins for healthy lowlanders at HA. In contrast, a lower abundance of glycolysis-associated protein alpha-enolase was observed, indicating curtailed glycolysis corroborating the plasma proteomics observations for HA [ 48 ]. In addition, a lower abundance of immunoglobulin receptor and prolactin-inducible protein was observed, further substantiating the utility of saliva proteins for HA research.…”

Section: Resultssupporting

confidence: 82%

Human adaptation to high altitude: a review of convergence between genomic and proteomic signatures

2022

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Both genomics- and proteomics-based investigations have identified several essential genes, proteins, and pathways that may facilitate human adaptive genotype/phenotype in a population-specific manner. This comprehensive review provides an up-to-date list of genes and proteins identified for human adaptive responses to high altitudes. Genomics studies for indigenous high-altitude populations like Tibetans, Andeans, Ethiopians, and Sherpas have identified 169 genes under positive natural selection. Similarly, global proteomics studies have identified 258 proteins (± 1.2-fold or more) for Tibetan, Sherpa, and Ladakhi highlanders. The primary biological processes identified for genetic signatures include hypoxia-inducible factor (HIF)-mediated oxygen sensing, angiogenesis, and erythropoiesis. In contrast, major biological processes identified for proteomics signatures include 14–3-3 mediated sirtuin signaling, integrin-linked kinase (ILK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and integrin signaling. Comparing genetic and protein signatures, we identified 7 common genes/proteins (HBB/hemoglobin subunit beta, TF/serotransferrin, ANGPTL4/angiopoietin-related protein 4, CDC42/cell division control protein 42 homolog, GC/vitamin D-binding protein, IGFBP1/insulin-like growth factor-binding protein 1, and IGFBP2/insulin-like growth factor-binding protein 2) involved in crucial molecular functions like IGF-1 signaling, LXR/RXR activation, ferroptosis signaling, iron homeostasis signaling and regulation of cell cycle. Our combined multi-omics analysis identifies common molecular targets and pathways for human adaptation to high altitude. These observations further corroborate convergent positive selection of hypoxia-responsive molecular pathways in humans and advocate using multi-omics techniques for deciphering human adaptive responses to high altitude.

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Section: Resultssupporting

confidence: 82%

Human adaptation to high altitude: a review of convergence between genomic and proteomic signatures

2022

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“…However, salivary DNA methylation patterns have been shown to correlate with DNA methylation from blood ( Thompson et al, 2013 ; Langie et al, 2016 ), intestinal mucosa ( Hearn et al, 2019 ), and the brain ( Smith et al, 2015 ). Furthermore, saliva panels have shown proteomic changes upon hypoxic exposure in cell cultures ( Jain et al, 2020 ), suggesting the relevance of this tissue for analyzing the overall hypoxic response. Therefore, we suggest that our analysis of saliva is an important first step in identifying DNA methylation changes to acute hypoxia that may be relevant to other bodily tissues.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide DNA Methylation Changes Associated With High-Altitude Acclimatization During an Everest Base Camp Trek

et al. 2021

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The individual physiological response to high-altitude hypoxia involves both genetic and non-genetic factors, including epigenetic modifications. Epigenetic changes in hypoxia factor pathway (HIF) genes are associated with high-altitude acclimatization. However, genome-wide epigenetic changes that are associated with short-term hypoxia exposure remain largely unknown. We collected a series of DNA samples from 15 participants of European ancestry trekking to Everest Base Camp to identify DNA methylation changes associated with incremental altitude ascent. We determined genome-wide DNA methylation levels using the Illumina MethylationEPIC chip comparing two altitudes: baseline 1,400 m (day 0) and elevation 4,240 m (day 7). The results of our epigenome-wide association study revealed 2,873 significant differentially methylated positions (DMPs) and 361 significant differentially methylated regions (DMRs), including significant positions and regions in hypoxia inducible factor (HIF) and the renin–angiotensin system (RAS) pathways. Our pathway enrichment analysis identified 95 significant pathways including regulation of glycolytic process (GO:0006110), regulation of hematopoietic stem cell differentiation (GO:1902036), and regulation of angiogenesis (GO:0045765). Lastly, we identified an association between the ACE gene insertion/deletion (I/D) polymorphism and oxygen saturation, as well as average ACE methylation. These findings shed light on the genes and pathways experiencing the most epigenetic change associated with short-term exposure to hypoxia.

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“…Saliva proteins have been implicated as possible markers for diagnosis of different diseases such as oral, lung and breast cancers, cardiovascular diseases, and systemic disorders. 26,27 Studies have not yet associated arsenic with PML.…”

Section: Socio-demographic Indicators Showed Thatmentioning

confidence: 99%

Evaluation of salivary protein patterns among a rural population exposed and non-exposed to arsenic-contaminated drinking water in areas of Tucumán (Argentina): a pilot study

et al. 2021

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Evaluation of salivary protein patterns among a rural population exposed and non-exposed to arsenic-contaminated drinking water in areas of Tucumán (Argentina): a pilot study Arsenic contamination in the environment and groundwater is a major global public health problem. Several researchers suggest that the toxicity of arsenic could be related to oral cancer development, usually resulting from potentially malignant lesions. During pathological processes, salivary proteins suffer modifications, which could lead to the discovery of new biomarkers. Objective: To analyze the protein profile in human saliva samples from a rural population exposed to high levels of arsenic in drinking water and its association with potentially malignant lesions. Methodology: This observational, analytic and cross-sectional design included 121 patients from the state of Graneros (Tucumán, Argentina). Arsenic concentration in drinking water was determined and, according to the values obtained, individuals were divided into 2 groups: exposed group and non-exposed group. Saliva samples were obtained, and total protein concentration was measured by Bradford method. Finally, Laemmli SDS-polyacrylamide gel electrophoresis was conducted to obtain the protein profile. Results: Total protein concentration in saliva was lower in the exposed group than in the non-exposed group. Average areas of 20 and 42 KDa bands were significantly lower in exposed group than non-exposed group. Conclusion: Chronic intake of high arsenic concentrations in drinking water produces changes in the salivary protein profile, which is associated with the presence of potentially malignant lesions.

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Saliva panel of protein candidates: A comprehensive study for assessing high altitude acclimatization

Cited by 8 publications

References 55 publications

Human adaptation to high altitude: a review of convergence between genomic and proteomic signatures

Human adaptation to high altitude: a review of convergence between genomic and proteomic signatures

Genome-Wide DNA Methylation Changes Associated With High-Altitude Acclimatization During an Everest Base Camp Trek

Evaluation of salivary protein patterns among a rural population exposed and non-exposed to arsenic-contaminated drinking water in areas of Tucumán (Argentina): a pilot study

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