TY - JOUR
T1 - DNA damage in astrocytes exposed to fumonisin B1
AU - Galvano, F.
AU - Campisi, A.
AU - Russo, A.
AU - Galvano, G.
AU - Palumbo, M.
AU - Renis, M.
AU - Barcellona, M. L.
AU - Perez-Polo, J. R.
AU - Vanella, A.
N1 - Funding Information:
This work was financially supported by grants from the MURST (Ministero dell’Università e della Ricerca Scientifica e Tecnologica), PRIN - Cofin 2000, Prof. F. Galvano, University of Reggio Calabria, Italy, and, in part, by grant from the MURST (ex 60%) 1999, Prof. A. Vanella, University of Catania, Italy, and MURST (ex 60%) 2000, Prof.ssa M. Renis, University of Catania, Italy.
PY - 2002
Y1 - 2002
N2 - Fumonisins are a group of toxic metabolites mainly produced by Fusarium moniliforme and Fusarium proliferatum, fungi that commonly occur on corn throughout the world. Fumonisin B1 (FB1), structurally resembling sphingoid bases, is an inhibitor of ceramide synthase, a key enzyme involved in de novo sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived from sphingolipid turnover. This inhibitory effect leads to accumulation of free sphinganine (SA) and sphingosine (SO), inducing cell death. However, little is known on the down stream effectors activated by these sphingolipids in the cell death signaling pathway. We exposed rat astrocytes to FB1 with the aim of evaluating the involvement of oxygen free radicals and of some other biochemical pathways such as caspase-3 activity and DNA damage. Our results indicate that FB1 treatment (48, 72 h and 6 days in vitro, DIV, and 10, 50, 100 μM) does not affect cell viability. Conversely, after 72 h of treatment, FB1 (50 and 100 μM) induced DNA damage and an enhancement of caspase-3 activity compared to controls. In addition, FB1 increased the expression of HSP70 at 10 and 50 μM at 48, 72 h, and 6 DIV of treatment. We conclude that DNA damage of apoptotic type in rat astrocytes is caused by FB1 and that the genotoxic potential of FB1 has probably been underestimated and should be reconsidered.
AB - Fumonisins are a group of toxic metabolites mainly produced by Fusarium moniliforme and Fusarium proliferatum, fungi that commonly occur on corn throughout the world. Fumonisin B1 (FB1), structurally resembling sphingoid bases, is an inhibitor of ceramide synthase, a key enzyme involved in de novo sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived from sphingolipid turnover. This inhibitory effect leads to accumulation of free sphinganine (SA) and sphingosine (SO), inducing cell death. However, little is known on the down stream effectors activated by these sphingolipids in the cell death signaling pathway. We exposed rat astrocytes to FB1 with the aim of evaluating the involvement of oxygen free radicals and of some other biochemical pathways such as caspase-3 activity and DNA damage. Our results indicate that FB1 treatment (48, 72 h and 6 days in vitro, DIV, and 10, 50, 100 μM) does not affect cell viability. Conversely, after 72 h of treatment, FB1 (50 and 100 μM) induced DNA damage and an enhancement of caspase-3 activity compared to controls. In addition, FB1 increased the expression of HSP70 at 10 and 50 μM at 48, 72 h, and 6 DIV of treatment. We conclude that DNA damage of apoptotic type in rat astrocytes is caused by FB1 and that the genotoxic potential of FB1 has probably been underestimated and should be reconsidered.
KW - Astrocytes
KW - Caspase-3
KW - DNA damage
KW - Fumonisin B
KW - Heat Shock Protein
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U2 - 10.1023/A:1014971515377
DO - 10.1023/A:1014971515377
M3 - Article
C2 - 11958538
AN - SCOPUS:0036204104
SN - 0364-3190
VL - 27
SP - 345
EP - 351
JO - Neurochemical Research
JF - Neurochemical Research
IS - 4
ER -