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Attenuation of MPTP/MPP(+) toxicity in vivo and in vitro by an 18-mer peptide derived from prosaposin.
Neuroscience. 2013 Apr 16; 236:373-93.N

Abstract

Parkinson's disease (PD) is a chronic progressive neurological disorder with an increasing incidence in the aging population. Neuroprotective and/or neuroregenerative strategies remain critical in the treatment of this increasingly prevalent disease. Prosaposin is a neurotrophic factor whose neurotrophic activity is attributed to a stretch of 12 amino acids located at the N-terminal region of saposin C. The present study was performed to investigate the protective effect and mechanism of action of a prosaposin-derived 18-mer peptide (PS18: LSELIINNATEELLIKGL) in Parkinson's disease models. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium ion (MPP(+))-induced dopaminergic neurotoxicity in C57BL/6J mice or SH-SY5Y cells and explored the protective effect and mechanisms of action of PS18 on dopaminergic neurons. Treatment with 2.0mg/kg PS18 significantly improved behavioral deficits, enhanced the survival of tyrosine hydroxylase-positive neurons, and decreased the activity of astrocytes in the substantia nigra and striatum in MPTP-induced PD model mice. In vitro, a Cell Counting Kit-8 assay and Hoechst 33258 staining revealed that co-treatment with 300ng/mL PS18 and 5mM MPP(+) protected against MPP(+)-induced nuclear morphological changes and attenuated cell death induced by MPP(+). We also found that PS18-FAM entered the cells, and the retention time of PS18-FAM in the cytoplasm of MPP(+)-treated cells was shorter than that of untreated cells. In addition, PS18 showed protection from MPP(+)/MPTP-induced apoptosis in the SH-SY5Y cells and dopaminergic neurons in the PD model mice via suppression of the c-Jun N-terminal kinase/c-Jun pathway; upregulation of Bcl-2; downregulation of BAX, attenuating mitochondrial damage; and inhibition of caspase-3. These findings suggest that PS18 may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative diseases such as PD.

Authors+Show Affiliations

Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23321539

Citation

Gao, H L., et al. "Attenuation of MPTP/MPP(+) Toxicity in Vivo and in Vitro By an 18-mer Peptide Derived From Prosaposin." Neuroscience, vol. 236, 2013, pp. 373-93.
Gao HL, Li C, Nabeka H, et al. Attenuation of MPTP/MPP(+) toxicity in vivo and in vitro by an 18-mer peptide derived from prosaposin. Neuroscience. 2013;236:373-93.
Gao, H. L., Li, C., Nabeka, H., Shimokawa, T., Saito, S., Wang, Z. Y., Cao, Y. M., & Matsuda, S. (2013). Attenuation of MPTP/MPP(+) toxicity in vivo and in vitro by an 18-mer peptide derived from prosaposin. Neuroscience, 236, 373-93. https://doi.org/10.1016/j.neuroscience.2013.01.007
Gao HL, et al. Attenuation of MPTP/MPP(+) Toxicity in Vivo and in Vitro By an 18-mer Peptide Derived From Prosaposin. Neuroscience. 2013 Apr 16;236:373-93. PubMed PMID: 23321539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuation of MPTP/MPP(+) toxicity in vivo and in vitro by an 18-mer peptide derived from prosaposin. AU - Gao,H L, AU - Li,C, AU - Nabeka,H, AU - Shimokawa,T, AU - Saito,S, AU - Wang,Z Y, AU - Cao,Y M, AU - Matsuda,S, Y1 - 2013/01/12/ PY - 2012/08/11/received PY - 2012/12/29/revised PY - 2013/01/08/accepted PY - 2013/1/17/entrez PY - 2013/1/17/pubmed PY - 2013/8/27/medline SP - 373 EP - 93 JF - Neuroscience JO - Neuroscience VL - 236 N2 - Parkinson's disease (PD) is a chronic progressive neurological disorder with an increasing incidence in the aging population. Neuroprotective and/or neuroregenerative strategies remain critical in the treatment of this increasingly prevalent disease. Prosaposin is a neurotrophic factor whose neurotrophic activity is attributed to a stretch of 12 amino acids located at the N-terminal region of saposin C. The present study was performed to investigate the protective effect and mechanism of action of a prosaposin-derived 18-mer peptide (PS18: LSELIINNATEELLIKGL) in Parkinson's disease models. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium ion (MPP(+))-induced dopaminergic neurotoxicity in C57BL/6J mice or SH-SY5Y cells and explored the protective effect and mechanisms of action of PS18 on dopaminergic neurons. Treatment with 2.0mg/kg PS18 significantly improved behavioral deficits, enhanced the survival of tyrosine hydroxylase-positive neurons, and decreased the activity of astrocytes in the substantia nigra and striatum in MPTP-induced PD model mice. In vitro, a Cell Counting Kit-8 assay and Hoechst 33258 staining revealed that co-treatment with 300ng/mL PS18 and 5mM MPP(+) protected against MPP(+)-induced nuclear morphological changes and attenuated cell death induced by MPP(+). We also found that PS18-FAM entered the cells, and the retention time of PS18-FAM in the cytoplasm of MPP(+)-treated cells was shorter than that of untreated cells. In addition, PS18 showed protection from MPP(+)/MPTP-induced apoptosis in the SH-SY5Y cells and dopaminergic neurons in the PD model mice via suppression of the c-Jun N-terminal kinase/c-Jun pathway; upregulation of Bcl-2; downregulation of BAX, attenuating mitochondrial damage; and inhibition of caspase-3. These findings suggest that PS18 may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative diseases such as PD. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/23321539/Attenuation_of_MPTP/MPP_+__toxicity_in_vivo_and_in_vitro_by_an_18_mer_peptide_derived_from_prosaposin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)00023-7 DB - PRIME DP - Unbound Medicine ER -