title: Regulation of gene expression in response to brain injury: enhanced expression and alternative splicing of rat prosaposin (SGP-1) mRNA in injured brain.
abstract: Prosaposin, the precursor of saposins or saps, is an injury-repair protein that acts on both neurons and glia. Previous studies identified the prosaposin gene as one of differentially expressed genes following nerve injury. In the present study, we investigated expression of prosaposin mRNA in injured brain utilizing rat models of focal cerebral ischemia and cortical stab wound in order to explore the significance of prosaposin in nerve injury. In ischemic brain, the level of prosaposin mRNA was elevated greater than 400% over controls within 5 days after ischemic insults. Importantly, this induction was accompanied by a 9-base splicing consistent with the alternative Exon-8 splicing of human prosaposin mRNA. In normal brain, two prosaposin mRNA species with and without the 9-base insertion were expressed at a ratio of 85:15; however, this equilibrium reverted to 5:95 following ischemic injury. Similar inductions were observed in stab wound brains. Immunohistochemical staining and in situ hybridization demonstrated an enhanced signal distribution of prosaposin mRNA and injury-induced prosaposin protein around the lesion. The data suggest the expression and processing of prosaposin mRNA may be crucially regulated not only for cerebral homeostasis but also during nerve regenerative and degenerative processes.
authors.affiliation: Department of Neurosciences, School of Medicine, Center for Molecular Genetics, University of California at San Diego, La Jolla, California 92093-0634, USA. mhiraiwa@ucsd.edu
authors.forename: Masao
authors.initials: M
authors.lastname: Hiraiwa
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Ai-Gang
authors.initials: AG
authors.lastname: Lu
authors.forename: Cui-Ying
authors.initials: CY
authors.lastname: Wang
authors.forename: Roberta
authors.initials: R
authors.lastname: Misasi
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Isao
authors.initials: I
authors.lastname: Hozumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Inuzuka
authors.forename: John S
authors.initials: JS
authors.lastname: O'Brien
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D015723:Gene Library; D006023:Glycoproteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049231:Saposins
chemical_list: D006023:Glycoproteins; C483345:PSAP protein, human; C483347:Psap protein, rat; D012333:RNA, Messenger; D049231:Saposins