TY - JOUR
T1 - Biological effects of inorganic arsenic onprimary cultures of rat astrocytes
AU - Di Liegro, Italia
AU - Schiera, Gabriella
AU - Proia, Patrizia
AU - Sciandrello, Giulia
AU - Catanzaro, Irene
AU - Caradonna, Fabio
AU - Catanzaro, Irene
AU - Schiera, Gabriella
AU - Sciandrello, Giulia
AU - Barbata, Giusi
AU - Di Liegro, Italia
AU - Caradonna, Fabio
AU - Barbata, Giuseppa
PY - 2010
Y1 - 2010
N2 - It is well established that inorganic arsenic induces neurotoxic effects and neurological defects in humans andlaboratory animals. The cellular and molecular mechanisms of its actions, however, remain elusive. Herein we report theeffects of arsenite (NaAsO2) on primary cultures of rat astrocytes.Cells underwent induction of heat shock protein 70 only at the highest doses of inorganic arsenic (30 and 60 μM),suggesting a high threshold to respond to stress. We also investigated arsenic genotoxicity with the comet assay.Interestingly, although cells treated with 10 μM arsenite for 24 h maintained >70% viability, with respect to untreatedcells, high DNA damage was already observed. Since arsenic is not known to be a direct-acting genotoxic agent, we investigated the possibility that its effects are due, in astrocytes as well, to ROS formation, as already described for other cell types. However, FACS analysis after CM-H2DCFDA staining did not evidence any significant increase of ROS production while, on the contrary, at the highest arsenite concentrations used, ROS production decreased. Concordantly, we found that, if most cells in the culture are still alive (i.e. up to 10 μM arsenite), they show a treatment-dependent increase in the concentration of SOD1. On the other hand, SOD2 concentration did not change. Finally, we found that astrocytes also synthesize PIPPin, an RNA-binding protein, the concentration of which was recently reported to change in response to stress induced by cadmium. Here we also report that, in cells exposed to high doses of arsenite, an anti-PIPPin antibody-positive faster migrating protein appears
AB - It is well established that inorganic arsenic induces neurotoxic effects and neurological defects in humans andlaboratory animals. The cellular and molecular mechanisms of its actions, however, remain elusive. Herein we report theeffects of arsenite (NaAsO2) on primary cultures of rat astrocytes.Cells underwent induction of heat shock protein 70 only at the highest doses of inorganic arsenic (30 and 60 μM),suggesting a high threshold to respond to stress. We also investigated arsenic genotoxicity with the comet assay.Interestingly, although cells treated with 10 μM arsenite for 24 h maintained >70% viability, with respect to untreatedcells, high DNA damage was already observed. Since arsenic is not known to be a direct-acting genotoxic agent, we investigated the possibility that its effects are due, in astrocytes as well, to ROS formation, as already described for other cell types. However, FACS analysis after CM-H2DCFDA staining did not evidence any significant increase of ROS production while, on the contrary, at the highest arsenite concentrations used, ROS production decreased. Concordantly, we found that, if most cells in the culture are still alive (i.e. up to 10 μM arsenite), they show a treatment-dependent increase in the concentration of SOD1. On the other hand, SOD2 concentration did not change. Finally, we found that astrocytes also synthesize PIPPin, an RNA-binding protein, the concentration of which was recently reported to change in response to stress induced by cadmium. Here we also report that, in cells exposed to high doses of arsenite, an anti-PIPPin antibody-positive faster migrating protein appears
KW - DNA damage
KW - PIPPin.
KW - astrocytes
KW - cell damage
KW - inorganic arsenic
KW - DNA damage
KW - PIPPin.
KW - astrocytes
KW - cell damage
KW - inorganic arsenic
UR - http://hdl.handle.net/10447/51421
M3 - Article
VL - 26
SP - 457
EP - 462
JO - International Journal of Molecular Medicine
JF - International Journal of Molecular Medicine
SN - 1107-3756
ER -