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Sphingolipids (SLs) have been implicated in numerous important cellular biologies; however, their study has been hindered by the complexities of SL metabolism. Furthermore, enzymes of SL metabolism represent a dynamic and interconnected network in which one metabolite can be transformed into other bioactive SLs through further metabolism, resulting in diverse cellular responses. Here we explore the effects of both lethal and sublethal doses of doxorubicin (Dox) in MCF-7 cells. The two concentrations of Dox resulted in the regulation of SLs, including accumulations in sphingosine, sphingosine-1-phosphate, dihydroceramide, and ceramide, as well as reduced levels of hexosylceramide.
A mistake was noticed between the Paper in Press and redacted article version regarding Scheme 2. The level of “SMS + CERT” activity was transposed onto the “Cdase (Golgi)” activity at some point in transitioning between the two versions. This has been corrected and activity is now representative of what is indicated in the figure legend.
Scheme 2SL metabolic flux rates in response to Dox. Rates are the calculated slope of label incorporation into the product analyte for a given enzymatic reaction during the time frames established in Figs. 2–5. The CDase enzymatic rates represent time points of the pulse concurrent with label metabolism in the Golgi (60–120 min). Treatments are indicated as follows: vehicle is black, cytostatic dose is blue, and cytotoxic dose is red. Units are pmol labeled product/nmol lipid Pi/min. Percentage vehicle is also given. ∗Rates that are significantly different from vehicle. CERT, ceramide transport protein; VT, vesicular trafficking.
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