Dihydroceramide desaturase activity is modulated by oxidative stress.
Idkowiak-Baldys J
et al.
Biochem J 2010 Mar;427(2)265-274
Idkowiak-Baldys J, Apraiz A, Li L, Rahmaniyan M, Clarke CJ, Kraveka JM, Asumendi A, Hannun YA.
Biochem J 2010 Mar;427(2)265-274
Abstract: Oxidative stress has been implicated previously in the regulation of ceramide metabolism. In the present study, its effects on dihydroceramide desaturase were investigated. To stimulate oxidative stress, HEK (human embyronic kidney)-293, MCF7, A549 and SMS-KCNR cells were treated with H2O2, menadione or tert-butylhydroperoxide. In all cell lines, an increase in dihydroceramide was observed upon oxidative stress as measured by LC (liquid chromatography)/MS. In contrast, total ceramide levels were relatively unchanged. Mechanistically, dihydroceramide desaturase activity was measured by an in situ assay and decreased in a time- and dose-dependent fashion. Interestingly, no detectable changes in the protein levels were observed, suggesting that oxidative stress does not induce degradation of dihydroceramide desaturase. In summary, oxidative stress leads to potent inhibition of dihydroceramide desaturase resulting in significant elevation in dihydroceramide levels in vivo.
The product of the MLD gene is a member of the membrane fatty acid desaturase family: overexpression of MLD inhibits EGF receptor biosynthesis.
Cadena DL
et al.
Biochemistry 1997 Jun;36(23)6960-6967
Cadena DL, Kurten RC, Gill GN.
Biochemistry 1997 Jun;36(23)6960-6967
Abstract: Membrane fatty acid desaturases are responsible for inserting double bonds into specific positions in fatty acids. We have cloned a new member of the human membrane fatty acid (lipid) desaturase gene family, MLD. The derived amino acid sequence of MLD contains three consensus motifs, HX3H, HX2HH, and HX2HHXFP, that are characteristic of a group of membrane fatty acid desaturases. MLD is predicted to be a multiple membrane-spanning protein and is found to be extractable from particulate fractions with detergent but not salt or urea. MLD is widely expressed in human tissues and is localized to the endoplasmic reticulum. Cotransfection of MLD with the epidermal growth factor (EGF) receptor resulted in decreased expression of the receptor but did not affect platelet-derived growth factor receptor expression. MLD overexpression inhibited biosynthesis of the EGF receptor, suggesting a possible role of a fatty acid desaturase in regulating biosynthetic processing of the EGF receptor.
