Poster Presentation AUS-oMicS 2025

The impact of dietary antioxidants on cysteine redox modifications in Diabetic Cardiomyopathy. (121122)

Molly Talbot 1 2 , Alexander Rookyard 1 3 4 , Desmond Li 3 4 5 , Jackie Zhou 1 2 , Stuart Cordwell 1 3 4 , Melanie White 1 2
  1. Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia
  2. School of Medical Science, University of Sydney, Camperdown, NSW, Australia
  3. School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW, Australia
  4. Sydney Mass Spectrometry , University of Sydney, Camperdown, NSW, Australia
  5. Heart Research Institute , Sydney , NSW, Australia

Overproduction of reactive oxygen species (ROS) is a key determinant in the pathogenesis of cardiac contractile dysfunction associated with type 2 diabetes and cardiovascular disease. Current pre-clinical evidence suggests that dietary antioxidant therapies can reduce ROS-mediated alterations to limit contractile dysfunction but the protein targets remain unknown. We aimed to identify redox-modified cysteine-containing peptides in the diabetic heart to identify sites protected by dietary antioxidants. We utilised a rat model of type 2 diabetes that combines high-fat diet (HFD) with a low-dose streptozotocin after 4-weeks of dietary intervention to induce a diabetic cardiomyopathy phenotype by the end of week 8. HFD were supplemented with either vitamin-A (8000IU/kg), -C (1000mg/kg), -E (0.84g/kg), or phytoestrogen (200mg/kg). Animal biometrics were monitored across the 8-week period including body weight, percentage adiposity, and blood glucose. Vitamin supplements were showed to reduce the degree of adiposity, despite similar average weight gain. In vivo cardiac contractility was measured by echocardiography, with antioxidants preserving left ventricular function. After 8-weeks, hearts were excised and perfused for 5 minutes by Langendorff. Two separate groups were delivered an acute infusion of either N-propionylglycine (MPG; 1mM) or N-acetylcysteine (0.4mM), selected for their antioxidant properties. Cys-containing peptides were isobarically labelled and enriched using thiol-disulfide exchange to perform quantitative redox proteomics using liquid chromatography tandem mass spectrometry (MS/MS). This study compares the capacity of dietary antioxidants to protect cardiac cysteine sites "at-risk" of redox modifications that impair cardiac contractility as a key pathological change in diabetic cardiomyopathy.