Neutral sphingomyelinase 2 induces dopamine uptake through regulation of intracellular calcium.

Authors: Kim, SK  Ahn, KH  Ji, JE  Choi, JM  Jeon, HJ  Jung, SY  Jung, KM  Kim, DK 
Citation: Kim SK, etal., Cell Signal. 2010 May;22(5):865-70. doi: 10.1016/j.cellsig.2010.01.012. Epub 2010 Jan 21.
Pubmed: (View Article at PubMed) PMID:20096352
DOI: Full-text: DOI:10.1016/j.cellsig.2010.01.012

Ceramide serves as a second messenger produced from sphingomyelin by the activation of sphingomyelinase (SMase). Here, we suggest that neutral SMase 2 (nSMase2) may regulate dopamine (DA) uptake. nSMase2 siRNA-transfected PC12 cells showed lower levels of nSMase activity and ceramide than scramble siRNA-transfected and control cells. Interestingly, transfection of nSMase2 siRNA or pretreatment with the nSMase2-specific inhibitor GW4869 resulted in decreased DA uptake. Reciprocally, exposure of PC12 cells to cell-permeable C(6)-ceramide induced a concentration-dependent increase in DA uptake. Removal of extracellular calcium by EGTA increased DA uptake in scramble-transfected and control cells, but not in nSMase2 siRNA-transfected or GW4869-pretreated cells. Moreover, siRNA-transfected cells showed higher levels of intracellular calcium than scramble cells, while C(6)-ceramide treatment resulted in decreased intracellular calcium compared to vehicle treatment alone. Taken together, these data suggest that nSMase2 may increase DA uptake through inducing ceramide production and thereby decreasing intracellular calcium levels.

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CRRD ID: 10041064
Created: 2015-05-11
Species: All species
Last Modified: 2015-05-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.