Premium
Disregulated Sphk1, Sphk2 and their receptors in the brain of MPTP‐induced mouse model of Parkinson's disease
Author(s) -
sivasubramanian meenalochani,
Dheen S Thameem,
Peng Zhao Feng,
Srinivasan Dinesh Kumar,
Tay Samuel SW
Publication year - 2012
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.26.1_supplement.920.6
Subject(s) - substantia nigra , sphingolipid , mptp , sphingosine , sphingosine kinase , dopaminergic , downregulation and upregulation , biology , sphingosine kinase 1 , microbiology and biotechnology , parkinson's disease , receptor , sphingosine 1 phosphate , neuroscience , dopamine , medicine , biochemistry , disease , gene
Sphingosine kinase (sphk) is a key enzyme responsible for phosphorylating sphingosine into sphingosine‐1‐phosphate(S1P). There are two forms of sphingokinases, Sphk1 and Sphk2. Sphingokinases in the nervous system control several signaling pathways involved in neuronal survival. In many neurodegenerative diseases, sphingolipid metabolism is highly disregulated. The present study demonstrates that the mRNA expression of Sphk1(a key enzyme of the sphingolipid metabolic pathway), its isoform Sphk2 and their five GPCRS (five G protein coupled receptors which are involved in the sphingolipid pathway) in dopaminergic neurons of the substantia nigra of the brain showed a marked decrease in the MPTP‐ induced mouse model of Parkinson's disease. Their downregulation was confirmed in MPP iodide‐treated MN9D cell line which contains dopaminergic neurons. Remarkably, the downregulation of these two sphingokinases was accompanied by a marked increase in the expression of TNF alpha. These results suggest that sphingolipid metabolism is altered in the substantia nigra of MPTP‐induced mouse model of Parkinson's disease. Relevance of these changes in the pathogenesis of Parkinson's disease will be discussed. Supported by grant no : MOE 2009‐T2‐1‐061 from the Ministry of Education, Singapore.