Carboxyfullerenes protect human keratinocytes from ultraviolet-B-induced apoptosis.
Carboxyfullerene, a water-soluble carboxylic acid derivative of a fullerene, which acts as a free-radical scavenger, was investigated as a protective agent against ultraviolet-light-induced damage in human keratinocytes. First, we demonstrate that carboxyfullerene is not cytotoxic for these cells. In addition, this compound significantly reduces the ultraviolet-B-induced inhibition of keratinocyte proliferation and protects keratinocytes from apoptosis caused by ultraviolet B irradiation in a time- and dose-dependent fashion. Furthermore, the percentage of cells with depolarized mitochondria is significantly lower in ultraviolet-B-irradiated keratinocytes pretreated with carboxyfullerene than in cells provided with diluent alone. Carboxyfullerene also protects human keratinocytes from apoptosis induced by exposure to deoxy-D-ribose, a sugar that causes cell death through a pathway involving oxidative stress. On the other hand, ultraviolet B downregulates bcl-2 levels in human keratinocytes, and carboxyfullerene fails to prevent this effect. These results suggest that carboxy- fullerene protects human keratinocytes from ultraviolet B damage possibly via a mechanism interfering with the generation of reactive oxygen species from depolarized mitochondria without the involvement of bcl-2.
Fumelli
C
C
Department of Neuropsychosensorial Pathology, Section of Dermatology, University of Modena and Reggio Emilia, Italy.
Marconi
A
A
Salvioli
S
S
Straface
E
E
Malorni
W
W
Offidani
A M
AM
Pellicciari
R
R
Schettini
G
G
Giannetti
A
A
Monti
D
D
Franceschi
C
C
Pincelli
C
C
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002244:Carbon / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000494:pharmacology*; D003855:Deoxyribose / Q000494:pharmacology; D005434:Flow Cytometry; D037741:Fullerenes; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology*; D008564:Membrane Potentials; D008928:Mitochondria; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays
D002264:Carboxylic Acids; D037741:Fullerenes; D019253:Proto-Oncogene Proteins c-bcl-2; D011837:Radiation-Protective Agents; D003855:Deoxyribose; D002244:Carbon; C069837:fullerene C60