Selective Reduction in α‐Hydroxypalmitic Acid‐containing Sphingomyelin and Concurrent Increase in Hydroxylated Ceramides in Murine Skin Tumors Induced by an Initiation‐promotion Regimen

The sphingomyelin cycle is activated to accumulate ceramides in the process of epidermal differentiation. We found that sphingomyelin in the epidermis of 4 different murine strains gave three bands on TLC, the lower band containing α‐hydroxypalmitic acid (C16h:0(α)). However, in the papillomas induced in the skin of SENCAR and SSIN mice by initiation with 7,12‐dimethylbenz[α] anthracene followed by promotion with 12‐O‐tetradecanoylphorbol acetate, the concentration of C16h:0(α)‐ containing sphingomyelin was selectively diminished with a concomitant increase in the concentrations of the ceramides containing α‐hydroxy fatty acids. These findings indicate a possible involvement of the selective hydrolysis of α‐hydroxy fatty acid‐containing sphingomyelin in the process of tumorigenesis in mouse skin.

[1]  K. Hirota,et al.  Alteration in the reactivity of sphingomyelin in mitogen-stimulated lymphocytes. , 1995, Journal of biochemistry.

[2]  Y. Hirabayashi,et al.  Induction of apoptotic DNA fragmentation and cell death by natural ceramide , 1995, FEBS letters.

[3]  R. Dobrowsky,et al.  Role of ceramide-activated protein phosphatase in ceramide-mediated signal transduction. , 1994, The Journal of biological chemistry.

[4]  A. Tuininga,et al.  Identification of molecular species of glycerophospholipids and sphingomyelin using electrospray mass spectrometry. , 1994, Journal of lipid research.

[5]  R. Kolesnick,et al.  The sphingomyelin pathway in tumor necrosis factor and interleukin-1 signaling , 1994, Cell.

[6]  S. Grant,et al.  Induction of apoptotic DNA damage and cell death by activation of the sphingomyelin pathway. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Y. Hannun,et al.  Sphingolipid breakdown products: anti-proliferative and tumor-suppressor lipids. , 1993, Biochimica et biophysica acta.

[8]  A. Bielawska,et al.  Selectivity of ceramide-mediated biology. Lack of activity of erythro-dihydroceramide. , 1993, The Journal of biological chemistry.

[9]  Y. Hannun,et al.  Programmed cell death induced by ceramide. , 1993, Science.

[10]  D. Johnson,et al.  Novel molecular species of sphingomyelin containing 2-hydroxylated polyenoic very-long-chain fatty acids in mammalian testes and spermatozoa. , 1992, The Journal of biological chemistry.

[11]  R. Kolesnick,et al.  Sphingomyelin synthesis is involved in adherence during macrophage differentiation of HL-60 cells. , 1991, The Journal of biological chemistry.

[12]  M. Iwamori,et al.  Enhancement of keratin synthesis induced by lipokeratinogenoside, N-(O-linoleoyl)-omega-hydroxy fatty acyl sphingosyl glucose, in association with alteration of the intracellular Ca(2+)-content and protein kinase in cultured keratinocytes (FRSK). , 1991, Journal of biochemistry.

[13]  Y. Hannun,et al.  Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gamma-interferon. Specific role in cell differentiation. , 1991, The Journal of biological chemistry.

[14]  A. Bielawska,et al.  Role of ceramide as a lipid mediator of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation. , 1990, The Journal of biological chemistry.

[15]  Y. Hannun,et al.  Sphingomyelin turnover induced by vitamin D3 in HL-60 cells. Role in cell differentiation. , 1989, The Journal of biological chemistry.

[16]  C. Sweeley,et al.  Quantitative analysis of carbohydrate residues of glycoproteins and glycolipids by gas—liquid chromatography , 1978 .

[17]  K. Karlsson,et al.  Studies on sphingosines. XIV. On the phytosphingosine content of the major human kidney glycolipids. , 1968, Biochimica et biophysica acta.

[18]  L. Obeid,et al.  The novel second messenger ceramide: identification, mechanism of action, and cellular activity. , 1993, Advances in lipid research.

[19]  W. L. Stahl Phospholipase C purification and specificity with respect to individual phospholipids and brain microsomal membrane phospholipids. , 1973, Archives of biochemistry and biophysics.