Subcellular alterations induced by UV-oxidized low-density lipoproteins in epithelial cells can be counteracted by alpha-tocopherol.
Oxidized LDL (ox-LDL) have been involved in the pathogenesis of several human diseases including dermatological pathologies. Oxidative modification of low-density lipoproteins (LDL) is accompanied by both extensive degradation of its polyunsaturated fatty acids and production of lipoperoxides. These highly reactive products induce an intracellular oxidative stress with a variety of cytotoxic effects. In order to evaluate cellular damage induced by oxidative stress in epidermal cells, a human epidermoid carcinoma cell line in culture (A 431) was used as experimental model. Cell treatment with UV-oxidized LDL resulted in cytostatic and cytotoxic effects characterized by morphological and functional alterations: inhibition of cell proliferation, modifications of cytoskeleton network, microtubular derangement, loss of cell-cell and cell-substrate contacts, cell detachment and cell death by apoptosis. The ox-LDL-induced alterations were almost completely prevented by pre-incubating cells with alpha-tocopherol. The results presented here could be of relevance for a better comprehension of the pathogenic mechanisms of several human diseases, including dermatological pathologies, and could indicate that antioxidants such as alpha-tocopherol could represent an important therapeutic challenge in the maintenance of cell and tissue homeostasis in the long run.
Masella
R
R
Department of Metabolism and Pathological Biochemistry, Istituto Superiore di Sanità, Rome, Italy. mbpsegr@net.iss.it
Straface
E
E
Giovannini
C
C
Di Benedetto
R
R
Scazzocchio
B
B
Viora
M
M
Cantafora
A
A
Malorni
W
W
D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology* / Q000528:radiation effects; D008855:Microscopy, Electron, Scanning; D018384:Oxidative Stress; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000494:pharmacology*
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E