Bleomycin induces caveolin-1 and -2 expression in epithelial lung cancer A549 cells.
BACKGROUND
Bleomycin induces apoptosis in alveolar epithelial cells. The expression of caveolin-1 and -2 in lung epithelial-derived A549 cells was analysed in terms of apoptosis after exposure to bleomycin.


METHODS
Apoptosis was investigated using flow cytometry, ELISA, immunohistochemistry and Western blot analysis. Caveolin-1 and -2 were determined at the protein level (Western blot). Intracellular caveolin-1 distribution was studied with immunofluorescence, as well as sucrose density gradient centrifugation.


RESULTS
Caveolin-1 and -2 were up-regulated 1 h after exposure to bleomycin and preceding the occurrence of caspase-8, and of caspase-3 and caspase-9 cleavage products. Sucrose density gradient centrifugation revealed that bleomycin exposure led to a partial translocation of caveolin-1 from caveolin-rich membrane fractions to non-raft fractions. Successful inhibition of bleomycin-induced apoptosis by the broad-spectrum caspase inhibitor zVAD-fmk did not influence the amount of caveolin-1 and -2.


CONCLUSIONS
The early up-regulation of caveolin-1 and -2 following bleomycin exposure is a rather apoptosis-independent event related to other unknown mechanisms of bleomycin-mediated cell injury.
Linge
Annett
A
Institute of Anatomy, Medical Faculty, Dresden University of Technology, Dresden, Germany.
Morishima
Nobuhiro
N
Kasper
Michael
M
Barth
Kathrin
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000494:pharmacology*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D051242:Caveolin 1 / Q000096:biosynthesis*; D051243:Caveolin 2 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; C495544:CAV2 protein, human; D061945:Caspase Inhibitors; D051242:Caveolin 1; D051243:Caveolin 2; D001761:Bleomycin; D053181:Caspase 8; D053453:Caspase 9