Programmed Cell Death Induced by Ceramide

American Association for the Advancement of Science (AAAS) - Tập 259 Số 5102 - Trang 1769-1771 - 1993
Lina M. Obeid1, Corinne M. Linardic1, Linda A. Karolak1, Yusuf A. Hannun1
1Department of Medicine, Duke University Medical Center, Durham, NC 27710.

Tóm tắt

Sphingomyelin hydrolysis and ceramide generation have been implicated in a signal transduction pathway that mediates the effects of tumor necrosis factor-α (TNF-α) and other agents on cell growth and differentiation. In many leukemic cells, TNF-α causes DNA fragmentation, which leads to programmed cell death (apoptosis). C 2 -ceramide (0.6 to 5 μM), a synthetic cell-permeable ceramide analog, induced internucleosomal DNA fragmentation, which was inhibited by zinc ion. Other amphiphilic lipids failed to induce apoptosis. The closely related C 2 -dihydroceramide was also ineffective, which suggests a critical role for the sphingolipid double bond. The effects of C 2 -ceramide on DNA fragmentation were prevented by the protein kinase C activator phorbol 12-myristate 13-acetate, which suggests the existence of two opposing intracellular pathways in the regulation of apoptosis.

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Tài liệu tham khảo

ALNEMRI, E.S., ACTIVATION OF INTERNUCLEOSOMAL DNA CLEAVAGE IN HUMAN CEM LYMPHOCYTES BY GLUCOCORTICOID AND NOVOBIOCIN - EVIDENCE FOR A NON-CA-2+-REQUIRING MECHANISM(S), JOURNAL OF BIOLOGICAL CHEMISTRY 265: 17323 (1990).

BRENNER, D.A., PROLONGED ACTIVATION OF JUN AND COLLAGENASE GENES BY TUMOR NECROSIS FACTOR-ALPHA, NATURE 337: 661 (1989).

DOBROWSKY, R.T., CERAMIDE STIMULATES A CYTOSOLIC PROTEIN PHOSPHATASE, JOURNAL OF BIOLOGICAL CHEMISTRY 267: 5048 (1992).

ELIAS, L, INDUCTION OF DIFFERENTIATION BY TUMOR-NECROSIS-FACTOR IN HL-60 CELLS IS ASSOCIATED WITH THE FORMATION OF LARGE DNA FRAGMENTS, LEUKEMIA 5: 879 (1991).

FLIEGER, D, ZN++ INHIBITS BOTH TUMOR NECROSIS FACTOR-MEDIATED DNA FRAGMENTATION AND CYTOLYSIS, INTERNATIONAL JOURNAL OF CANCER 44: 315 (1989).

GERSCHENSON, L.E., APOPTOSIS - A DIFFERENT TYPE OF CELL-DEATH, FASEB JOURNAL 6: 2450 (1992).

GOLDKORN, T, CERAMIDE STIMULATES EPIDERMAL GROWTH-FACTOR RECEPTOR PHOSPHORYLATION IN A431 HUMAN EPIDERMOID CARCINOMA-CELLS - EVIDENCE THAT CERAMIDE MAY MEDIATE SPHINGOSINE ACTION, JOURNAL OF BIOLOGICAL CHEMISTRY 266: 16092 (1991).

GUNJI, H, INTERNUCLEOSOMAL DNA FRAGMENTATION DURING PHORBOL ESTER INDUCED MONOCYTIC DIFFERENTIATION AND G0/G1 ARREST, JOURNAL OF CLINICAL INVESTIGATION 89: 954 (1992).

10.1126/science.2643164

KELER, T, SPECIFIC GROWTH-STIMULATION BY LINOLEIC-ACID IN HEPATOMA-CELL LINES TRANSFECTED WITH THE TARGET PROTEIN OF A LIVER CARCINOGEN, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 4830 (1992).

KERR, J. F. R., JOURNAL OF PATHOLOGY 107: 41 (1972).

KIM, M.Y., IDENTIFICATION OF SPHINGOMYELIN TURNOVER AS AN EFFECTOR MECHANISM FOR THE ACTION OF TUMOR-NECROSIS-FACTOR-ALPHA AND GAMMA-INTERFERON - SPECIFIC ROLE IN CELL-DIFFERENTIATION, JOURNAL OF BIOLOGICAL CHEMISTRY 266: 484 (1991).

MATHIAS, S, CHARACTERIZATION OF A CERAMIDE-ACTIVATED PROTEIN-KINASE - STIMULATION BY TUMOR-NECROSIS-FACTOR-ALPHA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88: 10009 (1991).

MCCONKEY, D.J., INHIBITION OF DNA FRAGMENTATION IN THYMOCYTES AND ISOLATED THYMOCYTE NUCLEI BY AGENTS THAT STIMULATE PROTEIN KINASE-C, JOURNAL OF BIOLOGICAL CHEMISTRY 264: 13399 (1989).

MERRILL, A.H., AN UPDATE OF THE ENZYMOLOGY AND REGULATION OF SPHINGOMYELIN METABOLISM, BIOCHIMICA ET BIOPHYSICA ACTA 1044: 1 (1990).

MERRILL, A.H., ENZYMES OF CERAMIDE BIOSYNTHESIS, METHODS IN ENZYMOLOGY 209: 427 (1992).

MERRILL, A.H., CERAMIDE - A NEW LIPID 2ND MESSENGER, NUTRITION REVIEWS 50: 78 (1992).

10.1126/science.1352911

OKAZAKI, T, SPHINGOMYELIN TURNOVER INDUCED BY VITAMIN-D3 IN HL-60 CELLS - ROLE IN CELL-DIFFERENTIATION, JOURNAL OF BIOLOGICAL CHEMISTRY 264: 19076 (1989).

OKAZAKI, T, ROLE OF CERAMIDE AS A LIPID MEDIATOR OF 1-ALPHA,25-DIHYDROXYVITAMIN-D3-INDUCED HL-60 CELL-DIFFERENTIATION, JOURNAL OF BIOLOGICAL CHEMISTRY 265: 15823 (1990).

RUBIN, B.Y., CORRELATION BETWEEN THE ANTICELLULAR AND DNA FRAGMENTING ACTIVITIES OF TUMOR NECROSIS FACTOR, CANCER RESEARCH 48: 6006 (1988).

SCHMID, D.S., TARGET-CELL DNA FRAGMENTATION IS MEDIATED BY LYMPHOTOXIN AND TUMOR-NECROSIS-FACTOR, LYMPHOKINE RESEARCH 6: 195 (1987).

SCHUTZE, S, TUMOR-NECROSIS-FACTOR SIGNAL TRANSDUCTION - CELL-TYPE-SPECIFIC ACTIVATION AND TRANSLOCATION OF PROTEIN KINASE-C, JOURNAL OF IMMUNOLOGY 144: 2604 (1990).

Strauss, W. M., Current Protocols in Molecular Biology: 1 (1992).

TOMEI, L.D., INHIBITION OF RADIATION-INDUCED APOPTOSIS INVITRO BY TUMOR PROMOTERS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 155: 324 (1988).

TURINSKY, J, AMERICAN JOURNAL OF PHYSIOLOGY 261: E620 (1991).

VANVELDHOVEN, P.P., CHANGES IN BIOACTIVE LIPIDS, ALKYLACYLGLYCEROL AND CERAMIDE, OCCUR IN HIV-INFECTED CELLS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 187: 209 (1992).

WRIGHT, S.C., APOPTOSIS AND DNA FRAGMENTATION PRECEDE TNF-INDUCED CYTOLYSIS IN U937 CELLS, JOURNAL OF CELLULAR BIOCHEMISTRY 48: 344 (1992).

10.1038/284555a0

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American Association for the Advancement of Science (AAAS)

Tập 259 Số 5102

1769-1771

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