Apoptosis Induced by Inhibition of Contact with Extracellular Matrix in Mouse Collecting Duct Cells
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Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation and aspects of cell growth control. Detachment from the matrix epithelial cells induces programmed cell death, and this cell detachment induced apoptosis has been referred to as 'anoikis'. This study was undertaken to determine whether apoptosis is induced by inhibition of contact with extracellular matrix (ECM) in collecting duct cells and to investigate the signaling mechanisms of the process. Upon detachment from ECM, mouse inner medullary collecting duct cells (mIMCD-3) and mouse outer cortical collecting duct cells (M-1), which were derived from an SV40 transgenic mouse, entered into programmed cell death. Forced suspension of mIMCD-3 or M-1 cells did not affect the expression of Bcl-2-related proteins and did not activate c-Jun NH(2)-terminal kinase. Detachment of cells from ECM activated p38 mitogen-activated protein kinase (p38), but its inhibition with SB203580 did not protect cells from anoikis. Detachment of cells from matrix inhibited NF-kappaB activity, and the inhibition of NF-kappaB activity by overexpression of nonphosphorylatable I-kappaB increased detachment-induced apoptotic cell death in M-1 cells. Forced suspension of M-1 cells still activated p53 activity. Caspase-8 was activated during anoikis, but the time course of its activation was in accordance with DNA fragmentation. These results indicate that detachment from ECM induces apoptosis in the kidney collecting duct cells. Changes in expression levels of Bcl-2-related proteins or activation of JNK/p38 kinase are not critical for anoikis. Decrease in NF-kappaB activity and activation of p53 induced by inhibition of interaction with ECM play roles in anoikis in SV-40-transformed collecting duct cells. Caspase-8 is activated during detachment-induced apoptosis, the mechanisms of which are independent of activation of cell death receptors.
author list (cited authors)
Park, M. Y., Lee, R. H., Lee, S. H., & Jung, J. S.