Abstract
Overexpression of calbindin-D28k (CaBP-28 k) induces neurite outgrowth in dopaminergic neuronal cells and could provide some protection to dopaminergic neurons against the pathological process in Parkinson’s disease. Transgenic mice CaBP-28 k overexpression and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models were generated, and the effect of midbrain dopamine neurons in ethology was also assessed. Tyrosine hydroxylase (TH)-immunoreactive neurons were counted, and the concentration of total protein and dopamine (DA) of striatum corpora was measured in four animal models. Results showed that the positive TH cells, content of DA, and ability of ethology in MPTP-induced transgenic mice were significantly higher than that in MPTP-induced wild-type mice. The findings demonstrate that overexpression of CaBP-28 k could provide protection for DA neurons from neurodegeneration. It would provide a potential strategy in the treatment of Parkinson’s diseases.
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References
Polymeropulos MH, Higgins JJ, Golbe LI, Johnson WG, Ide SE, Di IG, Sanges G, Stenroos ES, Pho LT, Schaffer AA, Lazzarini AM, Nussbaum RL, Duvoisin RC (1996) Map** of a gene for Parkinson’s disease to chromosome 4q21-q23. Science 274:1197–1199
Baimbridge KG, Celio MR, Rogers JH (1992) Calcium-binding proteins in the nervous system. Trends Neurosci 15:303–308
Slemmer JE, de Zeeuw CI, Weber JT (2005) Don’t get too excited: mechanism of glutamate mediated Purkinje cell death. Prog Brain Res 148:367–390
Yamada T, McGeer PL, Baimbridge KG, McGeer EG (1990) Relative sparing in Parkinson’s disease of substantia nigra dopamine neurons containing calbindin-28 k. Brain Res 526:303–307
Reisner PD, Christakos S, Vanaman TC (1992) In vitro enzyme activation with calbindin-D28k, the vitamin D-dependent 28 kDa calcium binding protein. FEBS Let 297:127–131
Lavoie B, Parent A (1991) Dopaminergic neurons expressing calbindin in normal and parkinsonian monkeys. Neuroreport 2:601–604
Iacopino AM, Christakos S, German D, Sonsalla PK, Altar CA (1992) Calbindin-D28k-containing neurons in animal models of neurodegeneration: possible protection from excitotoxicity. Mol Brain Res 13:251–261
Ng MC, Iacopino AM, Quintero EM, Marches F, Sonsalla PK, Liang CL, Speciale SG, German DC (1996) The neurotoxin MPTP increases albindin-D28k levels in mouse midbrain dopaminergic neurons. Mol Brain Res 36:329–336
Airaksinen MS, Thoenen H, Meyer M (1997) Vulnerability of midbrain dopaminergic neurons in calbindin-D28k-deficient mice: lack of evidence for a neuroprotective role of endogenous calbindin in MPTP-treated and weaver mice. Eur J Neurosci 9:120–127
Choi WS, Lee E, Lim J, Oh YJ (2008) Calbindin-D28K prevents drug-induced dopaminergic neuronal death by inhibiting caspase and calpain activity. Biochem Biophys Res Commun 371:127–131
Janicke RU, Sprengart ML, Wati MR, Porter AG (1998) Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273:9357–9360
Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bcl-2: release of cytochrome from mitochondria blocked. Science 275:1129–1132
Lowry DH, Rosebrough HJ, Rarr AL (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275
Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Déglon N, Aebischer P (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models Parkinson’s disease. Science 290:767–773
Howard K (2003) First Parkinson gene therapy trial launches. Nat Biotech 21:1117–1118
Iacopino AM, Quintero ME, Miller EK (1994) Calbindin-D28k: a potential neuroprotective protein. Neurodegeneration 3:1–20
Bellido T, Huening M, Raval-Pandya M, Manolagas SC, Christakos S (2000) Calbindin-D28k is expressed in osteoblastic cells and suppresses their apoptosis by inhibiting caspase-3 activity. J Biol Chem 275:26328–26332
Acknowledgments
The research was financially supported by the National Natural Science Foundation of China (No. 31172171), the Natural Science Foundation of Jiangsu Province (No. BK2010180); the President Foundation of Xuzhou Medical College (No. 2010KJZ10), and Social Development Project of Xuzhou (No. XM09B116).
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Yuan, HH., Chen, RJ., Zhu, YH. et al. The Neuroprotective Effect of Overexpression of Calbindin-D28k in an Animal Model of Parkinson’s Disease. Mol Neurobiol 47, 117–122 (2013). https://doi.org/10.1007/s12035-012-8332-3
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DOI: https://doi.org/10.1007/s12035-012-8332-3