Integrated Transcriptomic and Proteomic Analysis of Human Eccrine Sweat Glands Identifies Missing and Novel Proteins

Na, Chan Hyun; Sharma, Neeraj; Madugundu, Anil K.; Chen, Ruiqiang; Aksit, Melis A.; Rosson, Gedge D.; Cutting, Garry R.

doi:10.1074/mcp.ra118.001101

Cited by 28 publications

(19 citation statements)

References 52 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PBC was initially developed from two observations: 1) monkey uricases are very unstable when purified (this is also true for both An29 and An12, but not other modern and ancestral uricases) and 2) clinical results showing that recombinant pig uricase elicited strong immune responses in human subjects supported the notion that incorporating portions of the monkey sequence into the pig sequence may diminish the immune response in human patients. This notion was highly speculative at the time, but appears to now be supported by the recent discovery of uricase protein expression based on human proteomic analyses ( Na et al 2019 ). The read-through of the two premature stop codons in the human transcript does not generate an enzymatically active protein as we demonstrated previously ( Kratzer et al 2014 ), but it may “teach” the human immune system that uricase-like peptides/proteins are benign.…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic Articulation of Uric Acid Evolution in Mammals and How It Informs a Therapeutic Uricase

Hoshino

Tran

et al. 2021

Molecular Biology and Evolution

View full text Add to dashboard Cite

The role of uric acid during primate evolution has remained elusive ever since it was discovered over 100 years ago that humans have unusually high levels of the small molecule in our serum. It has been difficult to generate a neutral or adaptive explanation in part because the uricase enzyme evolved to become a pseudogene in apes thus masking typical signals of sequence evolution. Adding to the difficulty is a lack of clarity on the functional role of uric acid in apes. One popular hypothesis proposes that uric acid is a potent antioxidant that increased in concentration to compensate for the lack of vitamin C synthesis in primate species ∼65 Ma. Here, we have expanded on our previous work with resurrected ancient uricase proteins to better resolve the reshaping of uricase enzymatic activity prior to ape evolution. Our results suggest that the pivotal death-knell to uricase activity occurred between 20 and 30 Ma despite small sequential modifications to its catalytic efficiency for the tens of millions of years since primates lost their ability to synthesize vitamin C, and thus the two appear uncorrelated. We also use this opportunity to demonstrate how molecular evolution can contribute to biomedicine by presenting ancient uricases to human immune cells that assay for innate reactivity against foreign antigens. A highly stable and highly catalytic ancient uricase is shown to elicit a lower immune response in more human haplotypes than other uricases currently in therapeutic development.

show abstract

Section: Discussionmentioning

confidence: 99%

Phylogenetic Articulation of Uric Acid Evolution in Mammals and How It Informs a Therapeutic Uricase

Hoshino

Tran

et al. 2021

Molecular Biology and Evolution

View full text Add to dashboard Cite

show abstract

“…It has been speculated that due to a low pKa and a small molecular size, lactate is capable of passive diffusion (Sato 1977;Sonner et al 2015). However, recent transcriptomic and proteomic analysis of human eccrine cells identified similarities in gene expression between the human kidney and sweat glands, indicating that many genes expressed within the cortex of the kidney are also expressed within eccrine glands (Na et al 2019). Of particular interest is the finding of solute carrier family (SLC) proteins previously only found in the kidneys.…”

Section: Lactatementioning

confidence: 99%

“…While urea is a small molecule able to diffuse through and/or between cell walls, recent literature suggests that eccrine glands may express localized urea transporter subtypes (Keller et al 2016;Na et al 2019;Xie et al 2017). The expression of urea transporter 1 isoform 1 (UT-1) at the transcriptome and proteome level suggests the facilitation of transmembrane urea movement (Keller et al 2016;Xie et al 2017).…”

Section: Ureamentioning

confidence: 99%

“…These findings suggest that with excess urea production, there may be an active mechanism of urea excretion through sweat. Additionally, the overlap in gene expression found between eccrine glands and kidneys may indicate that sweat is another way to excrete metabolic wastes (Na et al 2019), albeit the effectiveness of this function remains uncertain (Baker 2019).…”

Section: Ureamentioning

confidence: 99%

See 1 more Smart Citation

Physiological mechanisms determining eccrine sweat composition

2020

View full text Add to dashboard Cite

The purpose of this paper is to review the physiological mechanisms determining eccrine sweat composition to assess the utility of sweat as a proxy for blood or as a potential biomarker of human health or nutritional/physiological status. Methods This narrative review includes the major sweat electrolytes (sodium, chloride, and potassium), other micronutrients (e.g., calcium, magnesium, iron, copper, zinc, vitamins), metabolites (e.g., glucose, lactate, ammonia, urea, bicarbonate, amino acids, ethanol), and other compounds (e.g., cytokines and cortisol). Results Ion membrane transport mechanisms for sodium and chloride are well established, but the mechanisms of secretion and/or reabsorption for most other sweat solutes are still equivocal. Correlations between sweat and blood have not been established for most constituents, with perhaps the exception of ethanol. With respect to sweat diagnostics, it is well accepted that elevated sweat sodium and chloride is a useful screening tool for cystic fibrosis. However, sweat electrolyte concentrations are not predictive of hydration status or sweating rate. Sweat metabolite concentrations are not a reliable biomarker for exercise intensity or other physiological stressors. To date, glucose, cytokine, and cortisol research is too limited to suggest that sweat is a useful surrogate for blood. Conclusion Final sweat composition is not only influenced by extracellular solute concentrations, but also mechanisms of secretion and/or reabsorption, sweat flow rate, byproducts of sweat gland metabolism, skin surface contamination, and sebum secretions, among other factors related to methodology. Future research that accounts for these confounding factors is needed to address the existing gaps in the literature.

show abstract

“…The mRNA exist in co-purified protein complexes [ 31 ] or bound to secreted ribosomes [ 32 ], which partly protect the mRNA from degradation. It was also interesting to see that a large proportion of the EV-enriched sweat mRNAs are common to the transcriptome of the human eccrine gland [ 33 ]. GO analysis mostly shows enrichment in ribosomal components and translation but no clear cellular origin as most of the mRNAs identified tend to be ubiquitously expressed.…”

Section: Discussionmentioning

confidence: 99%

Characterization of nucleic acids from extracellular vesicle-enriched human sweat

et al. 2021

View full text Add to dashboard Cite

Background The human sweat is a mixture of secretions from three types of glands: eccrine, apocrine, and sebaceous. Eccrine glands open directly on the skin surface and produce high amounts of water-based fluid in response to heat, emotion, and physical activity, whereas the other glands produce oily fluids and waxy sebum. While most body fluids have been shown to contain nucleic acids, both as ribonucleoprotein complexes and associated with extracellular vesicles (EVs), these have not been investigated in sweat. In this study we aimed to explore and characterize the nucleic acids associated with sweat particles. Results We used next generation sequencing (NGS) to characterize DNA and RNA in pooled and individual samples of EV-enriched sweat collected from volunteers performing rigorous exercise. In all sequenced samples, we identified DNA originating from all human chromosomes, but only the mitochondrial chromosome was highly represented with 100% coverage. Most of the DNA mapped to unannotated regions of the human genome with some regions highly represented in all samples. Approximately 5 % of the reads were found to map to other genomes: including bacteria (83%), archaea (3%), and virus (13%), identified bacteria species were consistent with those commonly colonizing the human upper body and arm skin. Small RNA-seq from EV-enriched pooled sweat RNA resulted in 74% of the trimmed reads mapped to the human genome, with 29% corresponding to unannotated regions. Over 70% of the RNA reads mapping to an annotated region were tRNA, while misc. RNA (18,5%), protein coding RNA (5%) and miRNA (1,85%) were much less represented. RNA-seq from individually processed EV-enriched sweat collection generally resulted in fewer percentage of reads mapping to the human genome (7–45%), with 50–60% of those reads mapping to unannotated region of the genome and 30–55% being tRNAs, and lower percentage of reads being rRNA, LincRNA, misc. RNA, and protein coding RNA. Conclusions Our data demonstrates that sweat, as all other body fluids, contains a wealth of nucleic acids, including DNA and RNA of human and microbial origin, opening a possibility to investigate sweat as a source for biomarkers for specific health parameters.

show abstract

Integrated Transcriptomic and Proteomic Analysis of Human Eccrine Sweat Glands Identifies Missing and Novel Proteins

Cited by 28 publications

References 52 publications

Phylogenetic Articulation of Uric Acid Evolution in Mammals and How It Informs a Therapeutic Uricase

Phylogenetic Articulation of Uric Acid Evolution in Mammals and How It Informs a Therapeutic Uricase

Physiological mechanisms determining eccrine sweat composition

Characterization of nucleic acids from extracellular vesicle-enriched human sweat

Contact Info

Product

Resources

About