Dataset Information

Multi-omics profiling of lung samples from genetically diabetic pigs reveals reduced ALOX15 expression and impaired eicosanoid switching as mechanisms contributing to a proinflammatory milieu

ABSTRACT: To evaluate molecular consequences of insulin-deficient diabetes mellitus for lung tissue, we used clinically diabetic pig model of mutant INS gene induced diabetes of youth (MIDY). A multi-omics analysis combining in-depth data-independent acquisition proteomics, and targeted lipidomics revealed multiple dysregulated proteins and lipids and associated biological pathways in the MIDY lung.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Lung

DISEASE(S): Diabetes Mellitus

SUBMITTER: Bachuki Shashikadze

LAB HEAD: Thomas Fröhlich

PROVIDER: PXD038014 | Pride | 2024-07-01

REPOSITORIES: Pride

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Multi-omics analysis of diabetic pig lungs reveals molecular derangements underlying pulmonary complications of diabetes mellitus.

Shashikadze Bachuki B Flenkenthaler Florian F Kemter Elisabeth E Franzmeier Sophie S Stöckl Jan B JB Haid Mark M Riols Fabien F Rothe Michael M Pichl Lisa L Renner Simone S Blutke Andreas A Wolf Eckhard E Fröhlich Thomas T

Disease models & mechanisms 20240723 7

Growing evidence shows that the lung is an organ prone to injury by diabetes mellitus. However, the molecular mechanisms of these pulmonary complications have not yet been characterized comprehensively. To systematically study the effects of insulin deficiency and hyperglycaemia on the lung, we combined proteomics and lipidomics with quantitative histomorphological analyses to compare lung tissue samples from a clinically relevant pig model for mutant INS gene-induced diabetes of youth (MIDY) wi ...[more]

PMID: 38900131

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Project description:The Jumonji domaining-containing protein JMJD6 is a 2-oxoglutarate dependent dioxygenase that has been implicated in a broad range of biological functions. Cellular studies have implicated the enzyme in chromatin biology, transcription, DNA repair, mRNA splicing and co-transcriptional processing. Although not all studies agree, JMJD6 has been reported to catalyse both hydroxylation of lysine residues and demethylation of arginine residues. However, despite extensive study and the indirect implication of JMJD6 catalysis in many cellular processes, direct assignment of JMJD6 catalytic substrates has been limited. Examination of a site of reported prolyl hydroxylation within a lysine-rich region of the bromodomain protein BRD4 led us to conclude that hydroxylation was in fact on lysine and catalysed by Jmjd6. This prompted a wider search for JMJD6-catalysed protein modifications deploying mass spectrometric methods designed to identify novel substrate associations and facilitate analysis of lysine-rich regions by LC-MSMS. Using derivatization of lysine with propionic anhydride to improve the analysis of tryptic peptides and a pharmacological inhibitor of JMJD6 to stabilise enzyme/substrate associations, we report over 100 sites of JMJD6-catalysed lysyl hydroxylation on 48 protein substrates including 19 sites of hydroxylation on BRD4. Most hydroxylations were within lysine-rich regions that are predicted to be unstructured; in some multiple modifications were observed on adjacent lysine residues. Almost all of the JMJD6 substrates defined in this study have been associated with membraneless organelle formation. Taken together with findings implicating lysine-rich regions in subcellular partitioning by liquid-liquid phase separation, our findings raise the possibility that JMJD6 may play a role in regulating such processes in response to stresses, including hypoxia. Note, this dataset corresponds to Figure 3 of the published manuscript; which employs a substrate-trapping methodology to identify novel substrates of JMJD6 by label free DIA approach.

			Action	DRS
	DIA-NN_output_precursors.tsv	Tabular
	LungPool_GPF_1.raw	Raw
	LungPool_GPF_2.raw	Raw
	LungPool_GPF_3.raw	Raw
	LungPool_GPF_4.raw	Raw