Plenary Lecture
The Neurotrophic Roles of Extracellular Guanosine
Associate Professor Shucui Jiang
Department of Surgery (Neurosurgery, Neurobiology)
Head of Hamilton NeuroRestorative Group
McMaster University, HSC 4E15
Ontario, Canada
E-mail: jiangs@mcmaster.ca
Abstract: In addition to adenine-based purinergic intercellular signaling systems involving adenine, adenosine and adenosine phosphates, over the last 20 years analogous guanine-based systems have been identified. Most of these systems are involved in "trophic" effects which affect the growth, differentiation and survival of various cells. Guanine-based purinergic signaling specifically has been investigated in cells of the nervous system and muscle. Guanine-based purines are released from cells, and when cells are damaged the release increases substantially. Under conditions simulating ischemia, the extracellular concentration of guanine-based purines such as guanosine is as high or higher than that of their adenine-based counterpart, adenosine. To date, most of the effects of extracullular guanosine are long term ‘trophic’ influences—relating to growth, proliferation and survival of cells. Recently, we discovered that guanosine may have potentially important implications for the biology of the nervous system. First, extracellular guanosine, unlike adenosine, does not cause apoptosis and actually protects against apoptosis caused by a number of stimuli through activation of the cell survival pathways such as MAPKinase and PI3Kinase/AKT. In addition to its neuroprotective activity, guanosine also improved motor behaviour and stimulated adult intrinsic progenitor/stem cells that assist in the restoration of function in both chronic spinal cord injury and a proteasome-induced chronic Parkinson’s model. There is evidence that, in some cases, guanosine produces its effects by entering cells and interacting with neurotrophic factors. However, there is further evidence that guanosine may interact with unique receptors on the surface of cells as well. Moreover, guanosine is metabolized to guanine by the enzyme purine nucleoside phosphorylase (PNP). Experimental studies have indicated that exogenous extracellular guanosine is relatively persistent compared with adenosine, but a large proportion of guanosine is metabolized to guanine. Emerging evidence indicates that guanine may also have its own extracellular signaling system that is distinct from guanosine. This would be of particular interest since guanine deaminase, the enzyme that metabolizes guanine, shows 50-fold regional variations in the brain. This degree of regional variation is characteristically associated with enzymes that degrade neurotransmitters. It appears that the concept of intercellular signaling by guanine-based purines is now well substantiated. Since GTP, GMP, guanosine and guanine have different biological effects, different receptive mechanisms and likely different signal transduction mechanisms, we are presented with an intriguing theory that the extracellular interconversion of these guanine derivatives provides an extra layer of intercellular signal regulation.
Brief Biography of the Speaker: Dr. Jiang graduated with a medical degree and undertook postgraduate clinical training and specialized as a Pathologist in China. Then she obtained M.Sc. in Biophysics in Shanghai and a Ph.D in Neurobiology from the Federal Institute for Neurobiology in Germany. She undertook her postdoctoral training at McMaster University and won a national award for research excellence. Her research program addresses the mechanisms responsible for the neuroprotection and neurorestoration following central nervous disorders, particularly, stroke and spinal cord injury. Currently, Dr. Jiang is an associate professor in Neurosurgery and Neurobiology, and the head of Hamilton NeuroRestorative Group (NRG). She is author of over 90 papers published in international journals and invited book chapters. She has been frequently invited to present her work nationally and internationally. She is on the Editorial Board of the European J Inflammation, and a reviewer for a large number of scientific journals and a member of committee and external reviewers for national and international peer-review grant agencies.