{
  "abstract": "Introduction Ischaemic heart disease is the leading cause of morbidity and mortality worldwide. During myocardial infarction, occlusion of the coronaries reduces blood flow to the heart causing ischaemic injury and eventual cell death. Restoration of blood flow by percutaneous coronary intervention and/or thrombolytics, can paradoxically lead to further myocardial damage and cell death. The extent of ischaemic- reperfusion (IR) injury determines the size of the infarct and the subsequent recovery of the patient, therefore understanding the molecular mechanisms responsible for IR injury is vital in developing novel therapeutic approaches. Initial events in IR injury include metabolic acidosis, followed by Na+ and Ca2+ overload inside the myocyte. Elevated Ca2+ prompts opening of the mitochondrial transition pore (mPTP), triggering release of coenzyme A (CoA) into the cytoplasm where it is made into palmitoyl CoA. This can be utilised by zDHHC-PATs, zDHHC5 in particular, to palmitoylate membrane proteins at the cell surface. This hyper- palmitoylation event drives a process called massive endocytosis (MEND), where ca. 70% of the plasma membrane becomes engulfed, resulting in cell damage and death.Aim The aim of this study was to determine the changes that occur in the cardiac palmitome following IR injury, in the presence and absence of cyclosporine A (an inhibitor of the mPTP) by quantitative proteomics.Methods The hearts of male rats were perfused respective to three different conditions to mimic ischaemic reperfusion injury with and without treatment with CsA. The ventricles were frozen and analysed using Acyl-RAC. The triptic peptides were isolated and were sent for analysis by mass spectrometry.Abstract BS50 Table 1Rat Heart Perfusion ConditionsResults and Conclusion The data revealed that 87 proteins had increased palmitoylation under IR conditions. Of these, the increase in palmitoylation on IR could be blocked for 27 proteins with CsA treatment, suggesting that their palmitoylation may be linked to opening of the mPTP. When the biological function of the CsA sensitive proteins was considered, three proteins were identified that may play an important role in IR injury, namely PACSIN3 (plays a role in endocytosis and possibly MEND), as well as Tescalcin and NHE1 (which may be responsible for the Na+ and Ca2+ overload).Abstract BS50 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Department of Cardiology, Queen Elizabeth Hospital, Glasgow G51 4TF"
      ],
      "name": "Astriti Vatwani"
    },
    {
      "affiliations": [
        "Clinical Lecturer (Teaching and Research), University of Dundee, DD1 4HN"
      ],
      "name": "Niall J Fraser"
    },
    {
      "affiliations": [
        "Professor of Molecular Physiology (Cardiovascular and Metabolic Health), University of Glasgow, G12 8QQ"
      ],
      "name": "Will Fuller"
    }
  ],
  "title": "BS50 Effects of ischaemic reperfusion injury on the cardiac palmitome in the presence and absence of cyclosporine A",
  "uid": "dbeaa4dc-7906-542d-8fc7-4ffe93d15c66"
}