Recombinant human granulocyte colony-stimulating factor protects against MPTP-induced dopaminergic cell death in mice by altering Bcl-2/Bax expression levels.

Abstract

Granulocyte colony-stimulating factor (G-CSF) has been used for the treatment of neutropenia in hematologic disorders. The neuroprotective effects of G-CSF were reported in neurological disease models. In the present study, we examined whether G-CSF can protect dopaminergic neurons against MPTP-induced cell death in a mouse model of Parkinson's disease. Mice of one group were injected intraperitoneally with MPTP for five consecutive days, those of another group with MPTP and intraperitoneal G-CSF at 2 days and 1 day before the first MPTP injection, and 30 min before each MPTP injection, while control mice received saline injections. Immunohistochemistry, western blotting analysis, and HPLC were performed to evaluate damage of substantia nigra dopaminergic neurons and expression of Bcl-2 and Bax protein. MPTP induced dopaminergic cell death in the substantia nigra. G-CSF significantly prevented MPTP-induced loss of tyrosine hydroxylase-positive neurons (p < 0.05), increased Bcl-2 protein and decreased Bax protein expression. Our findings indicate that G-CSF provides neuroprotection against MPTP-induced cell death and this effect is mediated by increasing Bcl-2 expression levels and decreasing Bax expression levels in C57BL/6 mice.

• Authors: Xu-Qing Cao, Hiroyuki Arai, Yong-Ri Ren, Hideki Oizumi, Ning Zhang, Shiho Seike, Tsuyoshi Furuya, Toru Yasuda, Yoshikuni Mizuno, Hideki Mochizuki
• Journal: Journal of neurochemistry (J Neurochem) Vol. 99 Issue 3 Pg. 861-7 (Nov 2006) ISSN: 0022-3042 [Print] England
• PMID: 17076657 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• bcl-2-Associated X Protein
• Granulocyte Colony-Stimulating Factor
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Tyrosine 3-Monooxygenase
• Dopamine

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (antagonists & inhibitors)
• Animals
• Cell Death (drug effects)
• Dopamine (physiology)
• Gene Expression (drug effects)
• Genes, bcl-2 (drug effects)
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Immunoblotting
• Immunohistochemistry
• In Situ Nick-End Labeling
• Male
• Mice
• Mice, Inbred C57BL
• Neostriatum (drug effects, metabolism)
• Parkinson Disease, Secondary (chemically induced, metabolism, pathology)
• Recombinant Proteins
• Tyrosine 3-Monooxygenase (metabolism)
• bcl-2-Associated X Protein (biosynthesis, genetics)