bims-prodis 2018-10-14 papers

Issue of 2018–10–14
four papers selected by
Nancy Gough, Bioserendipity

Toxicol In Vitro. 2018 Oct 03. pii: S0887-2333(18)30204-2. [Epub ahead of print]

Multi-omics analysis: Repeated exposure of a 3D bronchial tissue culture to whole-cigarette smoke.

Shinkichi Ishikawa, Kazushi Matsumura, Nobumasa Kitamura, Yuichiro Takanami, Shigeaki Ito.

Cigarette smoke (CS) is a major risk factor in the development of chronic inflammatory lung diseases such as chronic obstructive pulmonary disease. A comprehensive investigation of the biological impacts of chronic CS exposure on lung tissue is therefore important for understanding the pathogenesis of lung disease. We used three-dimensional (3D) organotypic human bronchial tissue cultures and metabolomics, transcriptomics, and proteomics to investigate changes in biological processes affected by repeated whole-CS exposure. We found that CS perturbed central carbon metabolism in relation with oxidative stress responses. Epidermal growth factor receptor, which is involved in the early-stage pathogenesis of airway diseases, was identified as a key regulator of the perturbed processes. Proteomic analysis of proteins in the apical surface liquid of the 3D bronchial tissue cultures indicated that repeated whole-CS exposure induced alterations in the secretion of several known biomarkers of airway diseases, including mucins and matrix metalloproteinases. These findings are consistent with observations from lung disease patients. Overall, our results suggest that 3D bronchial tissue cultures can provide valuable information on tissue-specific alterations in biological processes induced by chronic exposure to CS.

Keywords: Cigarette smoke; Epidermal growth factor receptor; Multi-omics analysis; Organotypic bronchial epithelium; Repeated exposure

DOI: https://doi.org/10.1016/j.tiv.2018.10.001

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Oct 02. pii: S1570-0232(18)31097-3. [Epub ahead of print]1100-1101 58-64

Development of a parallel microbore hollow fiber enzyme reactor platform for online 18O-labeling: Application to lectin-specific lung cancer N-glycoproteome.

Sun Young Lee, Seonjeong Lee, Sung Bum Park, Ki Young Kim, Jongki Hong, Dukjin Kang.

We introduce a simple online 18O-labeling protocol for protein samples that uses a parallelizing microbore hollow fiber enzyme reactor (mHFER) as an alternative tool for online proteolytic digestion. Online 18O-labeling is performed by separately attaching two mHFERs in parallel to a 10-port switching valve with a high-pressure syringe pump and two syringes containing 16O- or 18O-water. 16O-/18O-labeled peptides are formed in this manner and simultaneously analyzed online using nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS) without any residual trypsin activity. The usefulness of a parallel mHFER platform (P-mHFER) in 18O-labeling was tested using both cytochrome C and alpha-1-acid-glycoprotein to verify the incorporation level of two 18O atoms into tryptic peptides and to provide a quantitative assessment with varied mixing ratios. Additionally, our 18O-labeling approach was used to study the serum N-glycoproteome from lung cancer patients and controls to evaluate the applicability of lectin-based quantitative N-glycoproteomics. We successfully quantified 76 peptides (from 62 N-glycoproteins). Nineteen of these peptides from lung cancer serum were up-/down-regulated at least 2.5-fold compared to controls. As a result, the P-mHFER-based online 18O-labeling platform presented here can be a simple and reproducible way to allow quantitative proteomic analysis of diverse proteome samples.

Keywords: (18)O-labeling; Lung cancer; N-glycoproteins; Quantitative proteomics; mHFER

DOI: https://doi.org/10.1016/j.jchromb.2018.09.041

J Proteomics. 2018 Oct 04. pii: S1874-3919(18)30361-0. [Epub ahead of print]

Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease.

M Cañadas-Garre, K Anderson, J McGoldrick, A P Maxwell, A J McKnight.

Chronic kidney disease (CKD) is an aging-related disorder that represents a major global public health burden. Current biochemical biomarkers, such as serum creatinine and urinary albumin, have important limitations when used to identify the earliest indication of CKD or in tracking the progression to more advanced CKD. These issues underline the importance of finding and testing new molecular biomarkers that are capable of successfully meeting this clinical need. The measurement of changes in nature and/or levels of proteins and metabolites in biological samples from patients provide insights into pathophysiological processes. Proteomic and metabolomic techniques provide opportunities to record dynamic chemical signatures in patients over time. This review article presents an overview of the recent developments in the fields of metabolomics and proteomics in relation to CKD. Among the many different proteomic biomarkers proposed, there is particular interest in the CKD273 classifier, a urinary proteome biomarker reported to predict CKD progression and with implementation potential. Other individual non-invasive peptidomic biomarkers that are potentially relevant for CKD detection include type 1 collagen, uromodulin and mucin-1. Despite the limited sample sizes and variability of the metabolomics studies, some metabolites such as trimethylamine N-oxide, kynurenine and citrulline stand out as potential biomarkers in CKD.

Keywords: Chronic kidney disease; Diabetic kidney disease; Metabolomics; Proteomics

DOI: https://doi.org/10.1016/j.jprot.2018.09.020

Neurobiol Aging. 2018 Aug 25. pii: S0197-4580(18)30307-5. [Epub ahead of print]72 171-176

CSF pro-orexin and amyloid-β38 expression in Alzheimer's disease and frontotemporal dementia.

Wendy E Heywood, Jenny Hallqvist, Amanda J Heslegrave, Henrik Zetterberg, Chiara Fenoglio, Elio Scarpini, Jonathan D Rohrer, Daniela Galimberti, Kevin Mills.

There is an unmet need for markers that can stratify different forms and subtypes of dementia. Because of similarities in clinical presentation, it can be difficult to distinguish between Alzheimer's disease (AD) and frontotemporal dementia (FTD). Using a multiplex targeted proteomic LC-MS/MS platform, we aimed to identify cerebrospinal fluid proteins differentially expressed between patients with AD and FTD. Furthermore analysis of 2 confirmed FTD genetic subtypes carrying progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72) mutations was performed to give an insight into the differing pathologies of these forms of FTD. Patients with AD (n = 13) demonstrated a significant (p < 0.007) 1.24-fold increase in pro-orexin compared to FTD (n = 32). Amyloid beta-38 levels in patients with AD were unaltered but demonstrated a >2-fold reduction (p < 0.0001) in the FTD group compared to controls and a similar 1.83-fold reduction compared to the AD group (p < 0.001). Soluble TREM2 was elevated in both dementia groups but did not show any difference between AD and FTD. A further analysis comparing FTD subgroups revealed slightly lower levels of proteins apolipoprotein E, CD166, osteopontin, transthyretin, and cystatin C in the GRN group (n = 9) compared to the C9orf72 group (n = 7). These proteins imply GRN FTD elicits an altered inflammatory response to C9orf72 FTD.

Keywords: Alzheimer's disease; Amyloid β-38; C9orf72; Frontotemporal dementia; Orexin; Progranulin

DOI: https://doi.org/10.1016/j.neurobiolaging.2018.08.019