J. Neurochem. (2010) 113, 871–880.
Abstract
Many hemoglobin‐derived peptides are present in mouse brain, and several of these have bioactive properties including the hemopressins, a related series of peptides that bind to cannabinoid CB1 receptors. Although hemoglobin is a major component of red blood cells, it is also present in neurons and glia. To examine whether the hemoglobin‐derived peptides in brain are similar to those present in blood and heart, we used a peptidomics approach involving mass spectrometry. Many hemoglobin‐derived peptides are found only in brain and not in blood, whereas all hemoglobin‐derived peptides found in heart were also seen in blood. Thus, it is likely that the majority of the hemoglobin‐derived peptides detected in brain are produced from brain hemoglobin and not erythrocytes. We also examined if the hemopressins and other major hemoglobin‐derived peptides were regulated in the Cpefat/fat mouse; previously these mice were reported to have elevated levels of several hemoglobin‐derived peptides. Many, but not all of the hemoglobin‐derived peptides were elevated in several brain regions of the Cpefat/fat mouse. Taken together, these findings suggest that the post‐translational processing of alpha and beta hemoglobin into the hemopressins, as well as other peptides, is up‐regulated in some but not all Cpefat/fat mouse brain regions.