The human papillomavirus type 16 (HPV-16) E5 protein sensitizes human keratinocytes to apoptosis induced by osmotic stress.
We have studied the role of the HPV-16 E5 protein in apoptosis, using HaCaT cell lines stably transfected with either E5 (HaCaT/E5) or the empty vector (HaCaT/pMSG) as control. When subjected to a hyperosmolar concentration of sorbitol, HaCaT/E5 cells respond with cytochrome c release, activation of caspase-3, -8, and -9, and PARP-cleavage, showing that the mitochondria and death-receptor mediated apoptotic pathways are involved in subsequent cell death. Similar effects are observed for the control cells only after extended sorbitol treatment. Thus, E5-expressing cells are more sensitive to osmotic stress, perhaps because of modifications of the cellular membranes caused by this strongly hydrophobic molecule.
Kabsch
Kirsten
K
Deutsches Krebsforschungszentrum, Im Neuenheimer Feld-242, 69120 Heidelberg, Germany. k.kabsch@dkfz-heidelberg.de
Alonso
Angel
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003574:Cytochrome c Group / Q000032:analysis; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006982:Hypertonic Solutions / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009997:Osmotic Pressure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013012:Sorbitol / Q000494:pharmacology*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases; D000086082:Viroporin Proteins
D020169:Caspases; D016895:Culture Media, Serum-Free; D003574:Cytochrome c Group; D006982:Hypertonic Solutions; D020928:Mitogen-Activated Protein Kinases; D009856:Oncogene Proteins, Viral; D011065:Poly(ADP-ribose) Polymerases; D011993:Recombinant Fusion Proteins; D013012:Sorbitol; D048051:p38 Mitogen-Activated Protein Kinases; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins