Ceramide Mass Quantification Using the DG Kinase Assay

David K. Perry email me for information 

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1) extract lipids by the Bligh and Dyer method as follows:

a) suspend cell pellet in 0.4 ml of buffer and add to a 13 x 100 mm glass tube containing 1.5 ml of CHCl3/MeOH (1:2) and vortex

b) add 0.5 ml of CHCl3 and vortex

c) add 0.5 ml of H2O and vortex

d) centrifuge to separate phases and retain the lower phase (either discard the upper phase by aspiration or transfer the lower phase to a new 13 x 100 mm tube)

2) concentrate the lower phase by evaporating CHCl3 with N2 gas or by using speed vac. concentrator

3) construct a standard curve using 0-300 pmoles of natural ceramide from Avanti Polar Lipids and evaporate CHCl3

4) add 20 ml of b-OG/DOPG (7.5%:25mM) mixed micelles to the lipids in the experimental samples and to the ceramide standards and vortex vigorously

5) incubate for 30 min at 37° C and repeat vortexing

6) add 70 ml of reaction mixture containing the following: 50 ml of 2x buffer, 19.4 ml of dilution buffer, 0.2 ml of 1M DTT and 3-5 mg of a DG kinase membrane preparation (the non-lyophilized enzyme from Calbiochem gives best results)

7) add 10 ml of 10 mM [g-32P]-ATP (2 mCi/rxn) to each tube and allow rxn to proceed for 30 min at room temp.

8) stop rxn by the addition of 1.5 ml of CHCl3/MeOH (1:2)

9) add 0.3 ml of H2O and vortex

10) add 0.5 ml of CHCl3 and vortex

11) add 0.5 ml of 1% HClO4 and vortex

12) centrifuge to separate phases and retain lower phase

13) dry lower phase as previously described and suspend lipids in 30-40 ml of CHCl3/MeOH (4:1)

14) chromatograph 1/2 of total lipid on a silica gel 60 thin layer chromatography plate using a solvent system of CHCl3/acetone/MeOH/HOAc/H2O (10:4:3:2:1)

15) the [32P]-ceramide (ceramide 1-phosphate) is detected by using either a phosphorimager or by X-ray film

Notes:

The number of cells necessary to observe a ceramide signal with this assay varies with cell type but is usually around 106.

Ceramide 1-phosphate from the experimental samples is identified by its comigration with the phosphorylated ceramide standards.

Ceramide is quantitated using the phosphorimager or by scraping the [32P]-ceramide 1-phosphate from the TLC plates and performing liquid scintillation counting (ceramide quantitation is determined from the slope of the standard curve). The mass of ceramide 1-phosphate = the mass of ceramide assuming 100% conversion.

Initially, the assay should be validated by using the specific activity of the [32P]-ATP to determine the amount of ceramide in the ceramide standards. The assay is assumed valid if determination of ceramide by this method is at least 90% of the theoretical value of ceramide initially added.


 2x buffer

100 mM imidazole, pH 6.6

100 mM LiCl

25 mM MgCl2

2 mM EGTA, pH 6.6

 

dilution buffer

10 mM imidazole, pH 6.6

1 mM DTPA (diethylenetriaminepentaacetic acid)

 

Methodology Table of Contents

Biochemistry Home Page