Enhancement of TNF-alpha-induced apoptosis by immobilized arginine-glycine-aspartate: involvement of a tyrosine kinase-dependent, MAP kinase-independent mechanism.
Extracellular matrix facilitates anchorage-dependent cell survival via interaction of its arginine-glycine-aspartate (RGD) motif with integrins. In this report, we describe an unexpected, apoptosis-promoting the effect of immobilized RGD (iRGD) on tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. Mesangial cells cultured on RGD-coated plates showed enhanced susceptibility to TNF-alpha-induced apoptosis. iRGD alone did not affect cell survival. In contrast, iRGD did not facilitate but inhibited apoptosis induced by H(2)O(2). Mitogen-activated protein (MAP) kinases and tyrosine kinases are important mediators for the RGD-integrin signaling. Pretreatment with MAP kinase kinase inhibitor PD098059, c-Jun N-terminal kinase (JNK)-c-Jun/AP-1 inhibitor curcumin or p38 MAP kinase inhibitor SB203580 did not attenuate the apoptosis-promoting effect of iRGD. Consistently, transfection with dominant-negative mutants of extracellular signal-regulated kinases, JNK or p38 MAP kinase did not inhibit the effect of iRGD. In contrast, protein tyrosine kinase inhibitors, genistein, and herbimycin A, abrogated the apoptosis-promoting effect of iRGD. Of note, TNF-alpha-induced apoptosis on uncoated plates was not attenuated by tyrosine kinase inhibitors. These data provide the first evidence that iRGD accelerates certain apoptosis. We identified that the effect was mediated by the tyrosine kinase-dependent, MAP kinase-independent mechanism.
Moreno-Manzano
V
V
Department of Medicine, University College Medical School, University College London, Mortimer Street, London, W1T 3AA, United Kingdom.
Lucio-Cazana
J
J
Konta
T
T
Nakayama
K
K
Kitamura
M
M
D000818:Animals; D017209:Apoptosis; D016227:Benzoquinones; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005799:Genes, Dominant; D019833:Genistein / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D047029:Lactams, Macrocyclic; D020935:MAP Kinase Signaling System; D008858:Microscopy, Phase-Contrast; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D009154:Mutation; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017828:Rifabutin / Q000031:analogs & derivatives; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D047029:Lactams, Macrocyclic; D009842:Oligopeptides; D011725:Pyridines; D011809:Quinones; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; C020754:herbimycin; C047981:arginyl-glycyl-aspartic acid; D006861:Hydrogen Peroxide; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one