Prostaglandin D synthase isoforms from cerebrospinal fluid vary with brain pathology.
Glutathione independent prostaglandin D synthase (Swissprot P41222, PTGDS) has been identified in human cerebrospinal fluid and some changes in PTGDS in relation to disease have been reported. However, little is known of the extent that PTGDS isoforms fluctuate across a large range of congenital and acquired diseases. The purpose of this study was to examine changes in PTGDS isoforms in such a population. Spinal fluid from 22 healthy study participants (normal controls) with no classifiable neurological or psychiatric diagnosis was obtained and PTGDS isoforms were identified by specific immunostaining and mass spectrometry after denaturing 2D gel electrophoresis. The PTGDS isoforms in controls consisted of five charge isoforms that were always present and a small number of occasional, low abundance isoforms. A qualitative survey of 98 different people with a wide range of congenital and acquired diseases revealed striking changes. Loss of the control isoforms occurred in congenital malformations of the nervous system. Gain of additional isoforms occurred in some degenerative, most demyelinating and vasculitic diseases, as well as in Creutzfeldt-Jakob disease. A retrospective analysis of published data that quantified relative amounts of PTGDS in multiple sclerosis, schizophrenia and Parkinson's disease compared to controls revealed significant dysregulation. It is concluded that qualitative and quantitative fluctuations of cerebrospinal fluid PTGDS isoforms reflect both major and subtle brain pathophysiology.
Harrington
Michael G
MG
Molecular Neurology Program, Huntington Medical Research Institutes, 99 North El Molino Avenue, Pasadena, CA 91101, USA. mghworks@hmri.org
Fonteh
Alfred N
AN
Biringer
Roger G
RG
R Hühmer
Andreas F
AF
Cowan
Robert P
RP
D000595:Amino Acid Sequence; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001927:Brain Diseases / Q000175:diagnosis*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000134:cerebrospinal fluid*; D007527:Isoenzymes / Q000134:cerebrospinal fluid; D054834:Lipocalins; D008297:Male; D013058:Mass Spectrometry; D001523:Mental Disorders / Q000175:diagnosis*; D008969:Molecular Sequence Data
D007527:Isoenzymes; D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase