The role of RXFP1 and RXFP3 relaxin receptors in H2 and H3 relaxin-induced neuroprotection
LE3 .A278 2017
Bachelor of Science
Stroke is the leading cause of disability and third leading cause of death in Canada, resulting from ischemic conditions in the brain. Recent studies have indicated various tissues, including the brain, are protected by relaxin peptides during ischemic stress, making relaxins potential candidates as stroke therapeutics. H2 and H3 relaxinhave been shown to protect rat brain tissue from ischemic conditions, but little is known about the relaxin receptors involved. H2 and H3 relaxins interact with both RXFP1 and RXFP3 receptors, and both of these receptors are present in brain tissue. The purpose of the experiment was to study the role of RXFP1 and RXFP3 in mediating protective effects provided by relaxin peptides during oxygen and glucose deprived (OGD) stress in cultured brain slices. Brain slices from neonatal rats were cultured for two weeks. Subsequently, slices were exposed to one of seven treatments: oxygenated balanced salt solution with glucose (normoxic control; NC), oxygen and glucose deprived balanced salt solution (OGD control), or OGD media with: H2, H3, both H2 and H3, H2 and a RXFP3 antagonist (R3 B1-22R), or H3 and the RXFP3 antagonist. Propidium iodide (PI) fluorescence was used to highlight cellular damage and death. Mean counts of PI positive (PI+ve) cells were compared using ANOVA with Tukey’s post-hoc mean comparison test. Both relaxin peptides significantly reduced the number of PI+ve cells in OGD slices and the RXFP3 receptor antagonist only blocked the effect of H3. Western blots experiments were performed to confirm both relaxin receptors were present in neonatal rat brain tissue. Data suggests both RXFP1 and RXFP3 mediate actions of relaxin peptides in ischemic brain tissue. Further research is required to determine specific cell signaling pathways involved in neuroprotection provided by relaxin peptides.
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