Dataset Information

An Investigation of the Altered Textural Property in Woody Breast Myopathy Using an Integrative Omics Approach

ABSTRACT: The functionality/integrity of sarcoplasmic reticulum was compared between normal vs. myopathic woody breast tissues in Gallus gallus. Shotgun MS profiling of protein expression revealed an upregulation of calcium transport proteins and a downregulation of proteins responsible for calcium release. Findings supported a wider omics model for the underlying causes and effects of woody breast myopathy.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Gallus Gallus (chicken)

SUBMITTER: Steven Hartson

LAB HEAD: Michael D. Chao

PROVIDER: PXD031445 | Pride | 2022-05-19

REPOSITORIES: Pride

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Publications

An Investigation of the Altered Textural Property in Woody Breast Myopathy Using an Integrative Omics Approach.

Welter Amelia A AA Wu Wan Jun WJ Maurer Ryan R O'Quinn Travis G TG Chao Michael D MD Boyle Daniel L DL Geisbrecht Erika R ER Hartson Steve D SD Bowker Brian C BC Zhuang Hong H

Frontiers in physiology 20220317

Woody breast (WB) is a myopathy observed in broiler <i>Pectoralis major</i> (PM) characterized by its tough and rubbery texture with greater level of calcium content. The objective of this study was to investigate the functionality/integrity of WB sarcoplasmic reticulum (SR), which may contribute to the elevated calcium content observed in WB and other factors that may influence WB texture. Fourteen Ross line broiler PM [7 severe WB and 7 normal (N)] were selected, packaged, and frozen at -20°C ...[more]

PMID: 35370787

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Project description:SEPN1 is a type II protein of the endoplasmic reticulum (ER) whose loss of function gives rise to a collection of debilitating autosomal recessive myopathies gathered under the umbrella term of SEPN1-related myopathy (RM). At the moment, SEPN1-RM lacks an effective pharmacological treatment; thus, the medical management of the disease is only supportive. The potentially fatal diaphragmatic weakness leading to respiratory insufficiency in patients still ambulant is the main reason for medical concerns. Thus, studies on SEPN1-RM pathogenesis are necessary to implement a targeted pharmacological therapy aimed at relieving the general muscle weakness and the more worrisome diaphragmatic dysfunction. Here, we show a physical and functional interaction between SEPN1 and the ER stress mediator ERO1 alpha (henceforth, ERO1). Both SEPN1 and ERO1 are involved in the redox regulation of proteins into the ER, although in an opposite way SEPN1 imposes a less oxidant ER poise while ERO1 a more oxidant one, conceivable with a reductase function of SEPN1 and an oxidase one of ERO1. Furthermore, both are mainly localized in a region of the ER in close contact with mitochondria termed mitochondria-associated membranes (MAMs) and their loss impacts oppositely on the short-range MAMs, thereby impinging ER-mitochondria Ca2+ dynamics, OXPHOS, and bioenergetics. We find that ERO1 depletion restores the impaired short-range MAMs due to SEPN1 loss together with mitochondrial ATP. ERO1 knockout in a mouse background of SEPN1 loss blunts ER stress and the consequent Unfolded Protein Response (UPR) while it rescues the diaphragmatic weakness by improving ER/mitochondria contacts, calcium dynamics, and OXPHOS. Importantly, treatments of SEPN1 knock out mice with the chemical chaperone tauroursodeoxycholic acid (TUDCA) mimic the results of ERO1 loss improving calcium dynamics, OXPHOS, ER/mitochondria contacts, thereby rescuing diaphragmatic weakness as well. In addition, TUDCA-treated SEPN1-RM patients-derived myoblasts show a dynamic dose-dependent increase in ATP levels under ER stress conditions suggesting improved mitochondrial function. Thus, our findings point to the ERO1 axis in the pathogenesis of SEPN1-RM thereby impinging on MAMs and mitochondria bioenergetics and recall for the efficacy of a pharmacology therapy with ad hoc ER stress/ERO1 inhibitors for SEPN1-RM.

Dataset Information

An Investigation of the Altered Textural Property in Woody Breast Myopathy Using an Integrative Omics Approach

Publications

An Investigation of the Altered Textural Property in Woody Breast Myopathy Using an Integrative Omics Approach.

Similar Datasets

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