Tunicamycin preserves intercellular junctions, cytoarchitecture, and cell-substratum interactions in ATP-depleted epithelial cells.
Pretreatment with the nucleoside antibiotic tunicamycin was found to protect cultured renal epithelial cells in the face of ATP-depletion, in large part by preserving junctional and cellular architecture. Tunicamycin pretreatment of Madin-Darby canine kidney cells not only preserved E-cadherin staining at the plasma membrane, but also inhibited ATP-depletion-mediated E-cadherin degradation. Electron microscopic analysis, together with the preservation of the staining patterns of the tight junction marker ZO-1, the apical/microvillar marker gp135, and basolateral marker Na/K-ATPase suggested that tunicamycin preserved the junctional complex and the polarized epithelial cell phenotype. Tunicamycin pretreatment also prevented reductions in the filamentous actin content of the cells, as well as preserving Golgi architecture. Moreover, a quantitative measure of cell adhesion demonstrated that tunicamycin pretreatment resulted in a fivefold increase in attachment of cells to the substratum (77% versus 16%). Thus, pretreatment with tunicamycin protects polarized epithelial cells from ischemic injury through the preservation of epithelial cell architecture, intercellular junctions, and cell-substratum interactions in the setting of intracellular ATP-depletion.
Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, USA.
Sathish K
SK
George
Tobias N
TN
Meyer
Omaran
O
Abdeen
Kevin T
KT
Bush
Sanjay K
SK
Nigam
D000255:Adenosine Triphosphate / Q000172:deficiency*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D014415:Tunicamycin / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D014415:Tunicamycin; D000255:Adenosine Triphosphate