C3-fullero-tris-methanodicarboxylic acid protects cerebellar granule cells from apoptosis.
Buckminsterfullerenols were recently investigated for their protective properties in different models of acute and chronic neurodegeneration. We tested C3-fullero-tris-methanodicarboxylic acid in our in vitro model of apoptotic neuronal death, which consists of shifting the culture K+ concentration from 25 to 5 mM for rat cerebellar granule cells. The impairment of mitochondrial respiratory function as well as chromatin derangement and fragmentation of DNA in apoptotic oligonucleosomes that occur in these conditions were protected by this compound in a concentration-dependent way. To assess whether antioxidant activity could account for the rescue of cerebellar granule cells from apoptosis, we tested the fullerene derivative under FeSO4-induced oxidative stress and found significant protection. Thus, we visualized membrane and cytoplasmic peroxides and reactive oxygen species and found a significant reduction of the species after 24 h in 5 mM K+ with the fullerene derivative. Such evidence suggests that this compound exerts a protective role in cerebellar granule cell apoptosis, likely reducing the oxidative stress.
Bisaglia
M
M
Institute of Chemistry and Technology of Drugs, University of Perugia, Italy.
Natalini
B
B
Pellicciari
R
R
Straface
E
E
Malorni
W
W
Monti
D
D
Franceschi
C
C
Schettini
G
G
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010545:Peroxides / Q000378:metabolism; D011191:Potassium Deficiency / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; C120713:C(3)-fullero-tris-methanodicarboxylic acid; D003998:Dicarboxylic Acids; D018696:Neuroprotective Agents; D010545:Peroxides