Poster Presentation 22nd Annual Lorne Proteomics Symposium 2017

Physical activity elevates circulating levels of the neuroprotective LG3 peptide: potential novel stroke therapy? (#106)

Tony J Parker 1 2 , Crystal Reyes 1 2 , Daniel A Broszczak 1 2 , Catherine Davidson 1 2 , James A Broadbent 3 , Gregory Bix 4 5 6 , Jonathan Peake 1 2
  1. Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Qld, Australia
  2. School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Qld, Australia
  3. Sciex P/L, Brisbane, Qld, Australia
  4. Dept. of Neurology, University of Kentucky, Lexington, Kentucky, USA
  5. Dept. of Anatomy & Neurobiology, University of Kentucky, Lexington, Kentucky, USA
  6. Dept of Neurosurgery, Sanders Brown Centre on Aging, University of Kentucky, Lexington, Kentucky, USA

Stroke is a leading cause of death and disability globally and in Australia. Interestingly, physical activity and exercise is thought to reduce stroke risk and enhance rehabilitation following stroke, although the mechanisms remain unclear. Perlecan is a major ECM protein of vascular basement membranes, neuromuscular junctions and cartilage, which is known to be proteolytically processed to release a C-terminal bioactive fragment known as the laminin-type G3 (LG3) peptide. Importantly, the LG3 peptide is naturally released in the stroke-injured brain and is profoundly neuroprotective / neuroreparative when administered systemically in animals. Our research team has found that the LG3 peptide was significantly increased in the urine of physically active mining workers compared to sedentary controls. However, no previous studies have investigated the relationship between physical activity and changes in LG3 abundance in human serum where it might have therapeutic benefit. Therefore, the aim of this study was to measure the serum levels of LG3 fragments in response to exercise. Venous blood samples were collected at pre- and post-exercise from six well-trained male athletes who had participated in an intermittent, high-intensity trial (85% maximum aerobic capacity, VO2 max) and a continuous, moderate-intensity trial (60% VO2 max). Detection and quantification of LG3 was approached through the development of a Selected Reaction Monitoring (SRM) assay to specifically target LG3 peptide in serum. LG3 peptide levels significantly increased in response to moderate-intensity exercise (p = 0.026). The findings of this study suggest that circulating levels of the neuroprotective / neuroreparative LG3 peptide can be significantly increased under normal physiological conditions in healthy individuals following moderate exercise. In the future the results of this study may help establish a baseline level of physical activity required to induce elevated levels of the LG3 peptide in the blood which may have clinical utility.