Protective role of tissue transglutaminase in the cell death induced by TNF-alpha in SH-SY5Y neuroblastoma cells.
Tissue transglutaminase (tTGase) regulates various biological processes, including extracellular matrix organization, cellular differentiation, and apoptosis. Here we report the protective role of tTGase in the cell death that is induced by the tumor necrosis factor alpha (TNF-alpha) and ceramide, a product of the TNF-alpha signaling pathway, in human neuroblastoma SH-SY5Y cells. Treatment with retinoic acid (RA) induced the differentiation of the neuroblastoma cells with the formation of extended neurites. Immunostaining and Western blot analysis showed the tTGase expression by RA treatment. TNF-alpha or C(2) ceramide, a cell permeable ceramide analog, induced cell death in normal cells, but cell death was largely inhibited by the RA treatment. The inhibition of tTGase by the tTGase inhibitors, monodansylcadaverine and cystamine, eliminated the protective role of RA-treatment in the cell death that is caused by TNF-alpha or C(2)-ceramide. In addition, the co-treatment of TNF-alpha and cycloheximide decreased the protein level of tTGase and cell viability in the RA-treated cells, supporting the role of tTGase in the protection of cell death. DNA fragmentation was also induced by the co-treatment of TNF-alpha and cycloheximide. These results suggest that tTGase expressed by RA treatment plays an important role in the protection of cell death caused by TNF-alpha and ceramide.
Kweon
Soo-Mi
SM
Vascular System Research Center and Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chunchon, Kangwon 200-701, Korea.
Lee
Zee-Won
ZW
Yi
Sun-Ju
SJ
Kim
Young-Myeong
YM
Han
Jeong-A
JA
Paik
Sang-Gi
SG
Ha
Skwon-Soo
SS
D017209:Apoptosis / Q000187:drug effects*; D002103:Cadaverine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003538:Cystamine / Q000494:pharmacology; D019610:Cytoprotection; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002518:Ceramides; D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D003513:Cycloheximide; D011503:Transglutaminases; C008542:monodansylcadaverine; D002103:Cadaverine; D003538:Cystamine