Dataset Information

Mass spectrometry-based direct detection of multiple types of protein thiol modifications in pancreatic beta cells under endoplasmic reticulum stress

ABSTRACT: A 2D-LC-MS/MS strategy coupled with TMT-10 labeling was applied to mouse pancreatic beta cells (hetaTC-6) induced with ER stress by Thapsigargin to study the global proteome and protein cysteine PTM changes under ER stress. Samples were digested with trypsin, labeled with 10-plex TMT, then analyzed by LC-MS/MS. Data was searched with MS-GF+ using PNNL's DMS processing pipeline

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Wei-Jun Qian

PROVIDER: MSV000087543 | MassIVE | Sat May 29 20:39:00 BST 2021

SECONDARY ACCESSION(S): PXD026358

REPOSITORIES: MassIVE

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Publications

Mass spectrometry-based direct detection of multiple types of protein thiol modifications in pancreatic beta cells under endoplasmic reticulum stress.

Li Xiaolu X Day Nicholas J NJ Feng Song S Gaffrey Matthew J MJ Lin Tai-Du TD Paurus Vanessa L VL Monroe Matthew E ME Moore Ronald J RJ Yang Bin B Xian Ming M Qian Wei-Jun WJ

Redox biology 20210817

Thiol-based post-translational modifications (PTMs) play a key role in redox-dependent regulation and signaling. Functional cysteine (Cys) sites serve as redox switches, regulated through multiple types of PTMs. Herein, we aim to characterize the complexity of thiol PTMs at the proteome level through the establishment of a direct detection workflow. The LC-MS/MS based workflow allows for simultaneous quantification of protein abundances and multiple types of thiol PTMs. To demonstrate its utilit ...[more]

PMID: 34425387

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Project description:Myeloperoxidase (MPO), oxidative stress (OS), and endoplasmic reticulum (ER) stress are all increased in the lungs of neonatal rat pups raised in hyperoxia (HOX, >90% O2), an established model of bronchopulmonary dysplasia (BPD). However, the relationship between OS, MPO, and ER stress has not been examined in HOX rat pups. To determine the relationship between OS, MPO, and ER stress in BPD we treated Sprague-Dawley neonatal rat pups with Tunicamycin (Tun) or with HOX. Tun directly induces ER stress and simplifies neonatal lung alveolarization. Previously, we showed that HOX induces a cycle of destruction that we hypothesize through increased OS, MPO, and ER stress to induce BPD. To inhibit ER stress specifically, we used tauroursodeoxycholic acid (TUDCA), a molecular chaperone. To break the cycle of destruction and reduce OS and MPO we used N-acetyl-lysyltyrosylcysteine-amide (KYC), a systems pharmacology agent. Lung structure was studied morphometrically. ER stress was detected using immunofluorescence (IF), transcriptomic, proteomic, and electron microscopic analyses. Increased ER stress was observed in the lungs of HOX rat pups and also in human BPD lungs by IF. Morphometric and proteomic studies of rat lungs showed that Tun treatment decreased lung complexity and increased ER stress and BPD severity. The fact that TUDCA improved lung complexity in Tun-treated neonatal rat pups, and decreased BPD induced by HOX provides strong support for the idea that ER stress plays a causal role in BPD. Additional support comes from data showing TUDCA decreased lung myeloid cells and MPO levels in the lungs of both Tun- and HOX-treated neonatal rat pups. These data link OS and MPO to ER stress in the mechanisms mediating BPD. KYC's effective inhibition of ER stress in the lungs of Tun-treated rat pups provides additional support for the idea that MPO-induced ER stress plays a direct causal role in BPD. Thus, ER stress appears to expand our proposed cycle of destruction. Our results suggest ER stress evolves from OS and MPO to increase neonatal lung injury and impaired neonatal lung growth and development. The encouraging effect of TUDCA indicates chemical chaperone has the potential in treating BPD. Using multiomic data to investigate the role of endoplasmic reticulum stress in the development of BPD in rat model.

Dataset Information

Mass spectrometry-based direct detection of multiple types of protein thiol modifications in pancreatic beta cells under endoplasmic reticulum stress

Publications

Mass spectrometry-based direct detection of multiple types of protein thiol modifications in pancreatic beta cells under endoplasmic reticulum stress.

Similar Datasets

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