title: Lipocalin-type prostaglandin D synthase scavenges biliverdin in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage.
abstract: Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is the second major protein in human cerebrospinal fluid (CSF) and belongs to the lipocalin superfamily composed of various secretory lipophilic ligand transporter proteins. However, the endogenous ligand of L-PGDS has not yet been elucidated. In this study, we purified L-PGDS from the CSF of aneurysmal subarachnoid hemorrhage (SAH) patients. Lipocalin-type PG D synthase showed absorbance spectra with major peaks at 280 and 392 nm and a minor peak at around 660 nm. The absorbance at 392 nm of L-PGDS increased from 1 to 9 days and almost disappeared at 2 months after SAH, whereas the L-PGDS activity decreased from 1 to 7 days and recovered to normal at 2 months after SAH. These results indicate that some chromophore had accumulated in the CSF after SAH and bound to L-PGDS, thus inactivating it. Matrix assisted laser desorption ionization time-of-flight mass spectrometry of L-PGDS after digestion of it with endoproteinase Lys-C revealed that L-PGDS had covalently bound biliverdin, a by-product of heme breakdown. These results suggest that L-PGDS acted as a scavenger of biliverdin, which is a molecule not found in normal CSF. This is the first report of identification of a pathophysiologically important endogenous ligand for this lipocalin superfamily protein in humans.
authors.affiliation: 1] Department of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan [2] Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inui
authors.affiliation: Department of Neurosurgery and Restorative Neuroscience, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Mitsuhito
authors.initials: M
authors.lastname: Mase
authors.affiliation: Department of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Shirota
authors.affiliation: Department of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Nagashima
authors.affiliation: Department of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
mesh_terms: D017542:Aneurysm, Ruptured / Q000134:cerebrospinal fluid*; D001664:Biliverdine / Q000134:cerebrospinal fluid*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000134:cerebrospinal fluid*; D019746:Intramolecular Oxidoreductases / Q000134:cerebrospinal fluid*; D054834:Lipocalins / Q000134:cerebrospinal fluid*; D008297:Male; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid*; D013997:Time Factors
chemical_list: D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D001664:Biliverdine