An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia.

Abstract

It was previously reported that prosaposin possesses neurotrophic activity that is ascribed to an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain. To evaluate the effect of the 18-mer peptide on ischemic neuronal damage, the peptide was infused in the left lateral ventricle immediately after occlusion of the left middle cerebral artery (MCA) in stroke-prone spontaneously hypertensive (SP-SH) rats. The treatment ameliorated the ischemia-induced space navigation disability and cortical infarction and prevented secondary thalamic degeneration in a dose-dependent manner. In culture experiments, treatment with the 18-mer peptide attenuated free radical-induced neuronal injury at low concentrations (0.002 to 2 pg/mL), and the peptide at higher concentrations (0.2 to 20 ng/mL) protected neurons against hypoxic insult. Furthermore, a saposin C fragment comprising the 18-mer peptide bound to synaptosomal fractions of the cerebral cortex, and this binding decreased at the 1st day after MCA occlusion and recovered to the preischemic level at the 7th day after ischemia. These findings suggest that the 18-mer peptide ameliorates neuronal damage in vivo and in vitro through binding to the functional receptor, although the cDNA encoding prosaposin receptor has not been determined yet.

• Authors: K Igase, J Tanaka, Y Kumon, B Zhang, Y Sadamoto, N Maeda, S Sakaki, M Sakanaka
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 19 Issue 3 Pg. 298-306 (Mar 1999) ISSN: 0271-678X [Print] United States
• PMID: 10078882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycoproteins
• Peptide Fragments
• Psap protein, rat
• Saposins
• L-Lactate Dehydrogenase

Topics

• Amino Acid Sequence
• Animals
• Cells, Cultured
• Cerebral Arteries
• Cerebral Cortex (pathology)
• Cerebral Infarction (drug therapy, etiology)
• Glycoproteins (metabolism, therapeutic use)
• Ischemic Attack, Transient (complications, drug therapy, physiopathology)
• L-Lactate Dehydrogenase (metabolism)
• Molecular Sequence Data
• Movement Disorders (drug therapy, etiology)
• Neurons (drug effects, pathology, physiology)
• Peptide Fragments (chemistry, therapeutic use)
• Rats
• Rats, Inbred SHR
• Saposins
• Synaptosomes (metabolism)
• Thalamic Diseases (etiology, prevention & control)