Premium
Alteration in the sphingolipid metabolism leads to activation of the apoptotic cascade in the MPTP induced mouse model of Parkinson's disease
Author(s) -
Sivasubramanian Meenalochani,
Dheen S T,
Tay Samuel SW
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.533.8
Subject(s) - mptp , substantia nigra , sphingolipid , dopaminergic , parkinson's disease , microbiology and biotechnology , apoptosis , dopamine , biology , sphingosine , programmed cell death , neuroprotection , neuroscience , chemistry , medicine , biochemistry , disease , receptor
Parkinson's disease is a degenerative disorder of the central nervous system. It results from the death of dopaminergic neurons in the substantia nigra of the mid brain. Sphingolipids are important for neuronal survival. The sphingolipid metabolic pathway is regulated by two enzymes, namely Sphk1 and Sphk2. Sphk1 phosphorylates sphingosine leading to the formation of S1P which is essential for the survival of the neurons. The present study has demonstrated that both SPHK1 and its isoform SPHK2 in dopaminergic neurons of the substantia nigra of the brain showed a significant decrease in the MPTP‐induced mouse model of Parkinson's disease. This decrease was confirmed in both tissue samples and in the MN9D cell line treated with MPP + . Furthermore inhibition of the isoforms using dimethylsphingosine (DMS) leads to apoptosis of the neurons which was analysed using flow cytometry. Moreover Caspase 3 seems to increase significantly in both the MPP + and DMS treated groups. The present results suggest that, the alteration of sphingolipid metabolic pathway may be a cause for the death of dopaminergic neurons in the MPTP induced mouse model of Parkinson's disease. Supported by grant no: MOE 2009‐T2–1‐061 from the Ministry of Education, Singapore.