title: Cross talk between ceramide and redox signaling: implications for endothelial dysfunction and renal disease.
abstract: Recent studies have demonstrated that cross talk between ceramide and redox signaling modulates various cell activities and functions and contributes to the development of cardiovascular diseases and renal dysfunctions. Ceramide triggers the generation of reactive oxygen species (ROS) and increases oxidative stress in many mammalian cells and animal models. On the other hand, inhibition of ROS-generating enzymes or treatment of antioxidants impairs sphingomyelinase activation and ceramide production. As a mechanism, ceramide-enriched signaling platforms, special cell membrane rafts (MR) (formerly lipid rafts), provide an important microenvironment to mediate the cross talk of ceramide and redox signaling to exert a corresponding regulatory role on cell and organ functions. In this regard, activation of acid sphingomyelinase and generation of ceramide mediate the formation of ceramide-enriched membrane platforms, where transmembrane signals are transmitted or amplified through recruitment, clustering, assembling, or integration of various signaling molecules. A typical such signaling platform is MR redox signaling platform that is centered on ceramide production and aggregation leading to recruitment and assembling of NADPH oxidase to form an active complex in the cell plasma membrane. This redox signaling platform not only conducts redox signaling or regulation but also facilitates a feedforward amplification of both ceramide and redox signaling. In addition to this membrane MR redox signaling platform, the cross talk between ceramide and redox signaling may occur in other cell compartments. This book chapter focuses on the molecular mechanisms, spatial-temporal regulations, and implications of this cross talk between ceramide and redox signaling, which may provide novel insights into the understanding of both ceramide and redox signaling pathways.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. pli@vcu.edu
authors.forename: Pin-Lan
authors.initials: PL
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015398:Signal Transduction
chemical_list: D002518:Ceramides
references.citation: Free Radic Biol Med. 1993 Mar;14(3):287-93
references.pmid: 8458586
references.citation: Infect Immun. 2008 Oct;76(10):4405-13
references.pmid: 18663006
references.citation: J Hypertens. 1998 Nov;16(11):1659-65
references.pmid: 9856367
references.citation: Circ Res. 2001 Apr 27;88(8):824-31
references.pmid: 11325875
references.citation: Free Radic Biol Med. 2004 Jun 15;36(12):1496-504
references.pmid: 15182852
references.citation: Diabetes. 2009 May;58(5):1201-11
references.pmid: 19208908
references.citation: J Biol Chem. 1997 Jun 20;272(25):15642-9
references.pmid: 9188453
references.citation: Adv Lipid Res. 1993;25:65-90
references.pmid: 8368154
references.citation: Cell Mol Life Sci. 1999 May;55(5):707-34
references.pmid: 10379359
references.citation: Am J Physiol Heart Circ Physiol. 2002 Jan;282(1):H281-91
references.pmid: 11748073
references.citation: Dtsch Tierarztl Wochenschr. 1989 Apr;96(4):210-2
references.pmid: 2540948
references.citation: Antioxid Redox Signal. 2009 Apr;11(4):777-90
references.pmid: 18828708
references.citation: Kidney Int. 2004 Dec;66(6):2167-80
references.pmid: 15569306
references.citation: Arch Biochem Biophys. 2007 Mar 15;459(2):295-300
references.pmid: 17169322
references.citation: Helicobacter. 2006 Aug;11(4):266-71
references.pmid: 16882330
references.citation: Am J Respir Cell Mol Biol. 2001 Jun;24(6):762-8
references.pmid: 11415943
references.citation: J Immunol. 2008 Sep 15;181(6):4247-54
references.pmid: 18768882
references.citation: J Biol Chem. 2001 Dec 21;276(51):48269-75
references.pmid: 11585822
references.citation: Gen Physiol Biophys. 2004 Sep;23(3):265-95
references.pmid: 15638116
references.citation: Free Radic Biol Med. 2008 Apr 1;44(7):1443-51
references.pmid: 18242195
references.citation: Nat Med. 2007 Feb;13(2):164-70
references.pmid: 17259995
references.citation: Biochemistry (Mosc). 2001 Sep;66(9):1028-34
references.pmid: 11703187
references.citation: J Lipid Res. 2006 Apr;47(4):715-23
references.pmid: 16418538
references.citation: J Biol Chem. 2001 Jun 8;276(23):20589-96
references.pmid: 11279185
references.citation: J Lipid Res. 2003 May;44(5):869-77
references.pmid: 12639977
references.citation: Pol Merkur Lekarski. 2007 Oct;23(136):284-7
references.pmid: 18293852
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1223-8
references.pmid: 15142861
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1411-5
references.pmid: 17627466
references.citation: Biochem Soc Trans. 1996 Nov;24(4):1028-32
references.pmid: 8968506
references.citation: Circ Res. 2000 Mar 17;86(5):494-501
references.pmid: 10720409
references.citation: Radiology. 1998 Jul;208(1):103-10
references.pmid: 9646799
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1471-83
references.pmid: 17576159
references.citation: Am J Physiol. 1994 Jun;266(6 Pt 2):H2568-72
references.pmid: 8024019
references.citation: Am J Physiol. 1998 Mar;274(3):F587-95
references.pmid: 9530276
references.citation: Nature. 2000 Nov 9;408(6809):239-47
references.pmid: 11089981
references.citation: Mol Pharmacol. 2002 Dec;62(6):1446-55
references.pmid: 12435813
references.citation: Mol Pharmacol. 1999 Nov;56(5):867-74
references.pmid: 10531389
references.citation: Ann Med. 2007;39(4):275-89
references.pmid: 17558599
references.citation: Nihon Yakurigaku Zasshi. 2009 Sep;134(3):122-6
references.pmid: 19749482
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Jan;290(1):R96-R104
references.pmid: 16352863
references.citation: Am J Med. 2000 Apr 1;108(5):403-15
references.pmid: 10759097
references.citation: J Clin Invest. 1996 Apr 15;97(8):1916-23
references.pmid: 8621776
references.citation: FEBS Lett. 2002 Oct 30;531(1):47-53
references.pmid: 12401201
references.citation: J Biol Chem. 1998 May 1;273(18):11313-20
references.pmid: 9556624
references.citation: Cell Physiol Biochem. 2001;11(4):173-86
references.pmid: 11509825
references.citation: IUBMB Life. 2005 Apr-May;57(4-5):277-81
references.pmid: 16036611
references.citation: FASEB J. 2006 Jul;20(9):1501-3
references.pmid: 16754746
references.citation: Nature. 2005 Oct 6;437(7060):906-10
references.pmid: 16208376
references.citation: Biomed Pharmacother. 2005 May;59(4):169-74
references.pmid: 15862711
references.citation: Clin Exp Hypertens. 2009 Apr;31(2):156-78
references.pmid: 19330604
references.citation: Semin Cell Dev Biol. 2005 Aug-Oct;16(4-5):474-86
references.pmid: 15905109
references.citation: Oncogene. 2003 Oct 13;22(45):7070-7
references.pmid: 14557812
references.citation: J Biol Chem. 2005 May 13;280(19):19196-204
references.pmid: 15769735
references.citation: J Biol Chem. 2005 Jul 15;280(28):26467-76
references.pmid: 15883163
references.citation: Przegl Lek. 2001;58(10):915-8
references.pmid: 11957818
references.citation: Cell Physiol Biochem. 2007;20(6):909-18
references.pmid: 17982273
references.citation: Auton Neurosci. 2008 Nov 3;142(1-2):20-4
references.pmid: 18650132
references.citation: J Biol Chem. 1997 Jun 27;272(26):16281-7
references.pmid: 9195931
references.citation: Clin Exp Pharmacol Physiol. 2008 Apr;35(4):477-82
references.pmid: 18307745
references.citation: Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H954-62
references.pmid: 17028163
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1439-48
references.pmid: 17627472
references.citation: Curr Med Chem. 2004 May;11(9):1105-12
references.pmid: 15134509
references.citation: Biophys J. 2006 Sep 15;91(6):2172-83
references.pmid: 16815906
references.citation: Biochem Soc Trans. 2009 Oct;37(Pt 5):955-60
references.pmid: 19754431
references.citation: Int J Biochem Cell Biol. 2000 Feb;32(2):157-70
references.pmid: 10687951
references.citation: Biochim Biophys Acta. 2002 Dec 30;1585(2-3):139-45
references.pmid: 12531547
references.citation: Mol Immunol. 2002 Sep;38(16-18):1341-5
references.pmid: 12217405
references.citation: Hypertension. 2006 Jan;47(1):74-80
references.pmid: 16344372
references.citation: Antioxid Redox Signal. 2008 Jun;10(6):1061-77
references.pmid: 18321202
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1417-26
references.pmid: 17638544
references.citation: Oncogene. 2006 Sep 14;25(41):5612-25
references.pmid: 16636669
references.citation: Antioxid Redox Signal. 2010 Mar 15;12(6):703-12
references.pmid: 19761405
references.citation: PLoS One. 2010 Apr 21;5(4):e10189
references.pmid: 20422004
references.citation: Neurobiol Dis. 2006 Jul;23(1):178-89
references.pmid: 16626961
references.citation: J Biol Chem. 2006 May 12;281(19):13588-13595
references.pmid: 16537542
references.citation: Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):263-71
references.pmid: 18692605
references.citation: Proteomics. 2007 Jan;7(2):194-205
references.pmid: 17152095
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1519-34
references.pmid: 17576163
references.citation: J Biol Chem. 2004 Jun 4;279(23):24355-61
references.pmid: 15044445
references.citation: Biochim Biophys Acta. 2010 Apr;1803(4):482-91
references.pmid: 20036696
references.citation: Free Radic Biol Med. 2007 Apr 1;42(7):936-44
references.pmid: 17349922
references.citation: J Alzheimers Dis. 2004 Apr;6(2):165-9
references.pmid: 15096700
references.citation: Cell Mol Life Sci. 2009 Dec;66(23):3663-73
references.pmid: 19629388
references.citation: Proc Natl Acad Sci U S A. 1990 Jul;87(14):5578-82
references.pmid: 2164689
references.citation: Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):485-90
references.pmid: 18162606
references.citation: Am J Physiol Cell Physiol. 2006 Jan;290(1):C35-6
references.pmid: 16338978
references.citation: J Cell Mol Med. 2009 Sep;13(9B):3303-14
references.pmid: 20196779
references.citation: J Leukoc Biol. 2003 Aug;74(2):186-96
references.pmid: 12885935
references.citation: Curr Opin Nephrol Hypertens. 2002 Jan;11(1):87-92
references.pmid: 11753092
references.citation: Pharmacol Rep. 2009 Jan-Feb;61(1):99-104
references.pmid: 19307697
references.citation: J Virol. 2009 Oct;83(20):10605-15
references.pmid: 19706715
references.citation: Hypertension. 2009 Jan;53(1):90-6
references.pmid: 19029489
references.citation: Hypertension. 2008 Feb;51(2):481-7
references.pmid: 18195159
references.citation: Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H992-H1002
references.pmid: 20061541
references.citation: J Formos Med Assoc. 2009 Aug;108(8):599-611
references.pmid: 19666347
references.citation: Circulation. 2000 May 16;101(19):2302-8
references.pmid: 10811599
references.citation: Biochem Soc Trans. 2004 Nov;32(Pt 5):679-81
references.pmid: 15493986
references.citation: Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):2056-62
references.pmid: 18772496
references.citation: Kidney Int. 2004 Nov;66(5):1977-87
references.pmid: 15496169
references.citation: J Biol Chem. 1999 Nov 5;274(45):32512-9
references.pmid: 10542298
references.citation: Hepatology. 2010 May;51(5):1744-53
references.pmid: 20146263
references.citation: Biochim Biophys Acta. 2008 Jul;1783(7):1354-68
references.pmid: 18298957
references.citation: Hypertens Res. 2008 Feb;31(2):305-13
references.pmid: 18360051
references.citation: Exp Physiol. 2006 Sep;91(5):807-19
references.pmid: 16857720
references.citation: Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9
references.pmid: 11413487
references.citation: J Cardiovasc Pharmacol. 2006 Jan;47(1):158-63
references.pmid: 16424801
references.citation: Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1183-92
references.pmid: 16910766
references.citation: J Toxicol Environ Health B Crit Rev. 2008 Jan;11(1):1-15
references.pmid: 18176884
references.citation: Circ Res. 2002 May 17;90(9):1012-9
references.pmid: 12016268
references.citation: Biochim Biophys Acta. 2004 Jan 28;1660(1-2):164-70
references.pmid: 14757232
references.citation: Blood Press. 2008;17(2):70-7
references.pmid: 18568695
references.citation: Gene. 2001 May 16;269(1-2):131-40
references.pmid: 11376945
references.citation: Traffic. 2006 Jul;7(7):889-902
references.pmid: 16787399
references.citation: Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1337-45
references.pmid: 16115039
references.citation: J Med Invest. 2009 Feb;56(1-2):33-41
references.pmid: 19262012
references.citation: Circ Res. 2000 Feb 4;86(2):198-204
references.pmid: 10666416
references.citation: Diabetes Care. 2008 Feb;31 Suppl 2:S170-80
references.pmid: 18227481
references.citation: Free Radic Biol Med. 2000 Jun 15;28(12):1780-94
references.pmid: 10946220
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1499-518
references.pmid: 17600463
references.citation: Andrologia. 1998;30 Suppl 1:81-6
references.pmid: 9629447
references.citation: Eukaryot Cell. 2006 Mar;5(3):488-98
references.pmid: 16524904
references.citation: Ann Transplant. 2004;9(1):81-3
references.pmid: 15478900
references.citation: J Neurochem. 1999 Aug;73(2):675-83
references.pmid: 10428064
references.citation: Arch Biochem Biophys. 2002 Jan 15;397(2):342-4
references.pmid: 11795892
references.citation: J Membr Biol. 1998 Jul 15;164(2):103-14
references.pmid: 9662555
references.citation: Environ Health Perspect. 1994 Dec;102 Suppl 10:5-12
references.pmid: 7705305
references.citation: J Alzheimers Dis. 1998 Mar;1(1):45-55
references.pmid: 12214011
references.citation: Free Radic Res. 2010 Aug;44(8):831-42
references.pmid: 20528560
references.citation: Biochem Soc Trans. 2006 Nov;34(Pt 5):960-4
references.pmid: 17052237
references.citation: J Biol Chem. 1997 Aug 8;272(32):19943-50
references.pmid: 9242662
references.citation: Nat Rev Neurosci. 2007 Feb;8(2):128-40
references.pmid: 17195035
references.citation: Essays Biochem. 2007;43:17-27
references.pmid: 17705790
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1427-37
references.pmid: 17627468
references.citation: New Horiz. 1998 May;6(2):169-80
references.pmid: 9654324
references.citation: Antioxid Redox Signal. 2007 Jul;9(7):817-28
references.pmid: 17508908
references.citation: Cell Physiol Biochem. 2010;26(1):21-8
references.pmid: 20502001
references.citation: Cardiovasc Res. 1999 Aug 15;43(3):562-71
references.pmid: 10690328
references.citation: Antioxid Redox Signal. 2009 Jun;11(6):1313-33
references.pmid: 19072143
references.citation: Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1824-30
references.pmid: 15976327
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4262-5
references.pmid: 11917128
references.citation: FEBS J. 2009 Jun;276(12):3308-23
references.pmid: 19438725
references.citation: Pol Merkur Lekarski. 2007 Oct;23(136):280-3
references.pmid: 18293851
references.citation: Mol Cell Biochem. 2001 Mar;219(1-2):21-7
references.pmid: 11354249
references.citation: Nature. 1997 Jun 5;387(6633):569-72
references.pmid: 9177342
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1535-40
references.pmid: 17678446
references.citation: Antioxid Redox Signal. 2007 Sep;9(9):1457-70
references.pmid: 17661535
references.citation: Asian Pac J Cancer Prev. 2009 Oct-Dec;10(4):535-44
references.pmid: 19827865
references.citation: J Biol Chem. 2003 Aug 29;278(35):32744-52
references.pmid: 12801930
references.citation: Cardiovasc Res. 2011 Feb 1;89(2):401-9
references.pmid: 20823276