4.7 Article

A Blood Biomarker for Duchenne Muscular Dystrophy Shows That Oxidation State of Albumin Correlates with Protein Oxidation and Damage in Mdx Muscle

Journal

ANTIOXIDANTS
Volume 10, Issue 8, Pages -

Publisher

MDPI
DOI: 10.3390/antiox10081241

Keywords

biomarkers; Cys34 albumin; thiol oxidation; oxidative stress; Duchenne muscular dystrophy; mdx mice; ageing; exercise; taurine

Funding

  1. Duchenne UK
  2. Save Our Sons Duchenne Foundation (Australia)
  3. Muscular Dystrophy Western Australia
  4. French Muscular Dystrophy Association (AFM-Telethon)
  5. Higher Committee for Education Development in Iraq

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Research has shown that oxidation of albumin Cys34 is a sensitive blood biomarker that reflects oxidative stress in muscle tissue of DMD patients. Plasma albumin oxidation reflects muscle dystropathology, supporting its use as a blood biomarker to assist with advancing clinical development of therapies for DMD.
Duchenne muscular dystrophy (DMD) is a severe X-linked muscle wasting disease with no cure. While the precise mechanisms of progressive dystropathology remain unclear, oxidative stress caused by excessive generation of oxidants is strongly implicated. Blood biomarkers that could track oxidant levels in tissues would be valuable to measure the effectiveness of clinical treatments for DMD; our research has focused on developing such biomarkers. One target of oxidants that has the potential to be harnessed as a clinical biomarker is the thiol side chain of cysteine 34 (Cys34) of the blood protein albumin. This study using the mdx mouse model of DMD shows that in plasma, albumin Cys34 undergoes thiol oxidation and these changes correlate with levels of protein thiol oxidation and damage of the dystrophic muscles. A comparison with the commonly used biomarker protein carbonylation, confirmed that albumin thiol oxidation is the more sensitive plasma biomarker of oxidative stress occurring in muscle tissue. We show that plasma albumin oxidation reflects muscle dystropathology, as increased after exercise and decreased after taurine treatment of mdx mice. These data support the use of albumin thiol oxidation as a blood biomarker of dystropathology to assist with advancing clinical development of therapies for DMD.

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