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Biological effects of inorganic arsenic on primary cultures of rat astrocytes
- Source :
- International Journal of Molecular Medicine. 26
- Publication Year :
- 2010
- Publisher :
- Spandidos Publications, 2010.
-
Abstract
- It is well established that inorganic arsenic induces neurotoxic effects and neurological defects in humans and laboratory animals. The cellular and molecular mechanisms of its actions, however, remain elusive. Herein we report the effects 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 microM), suggesting a high threshold to respond to stress. We also investigated arsenic genotoxicity with the comet assay. Interestingly, although cells treated with 10 microM arsenite for 24 h maintained >70% viability, with respect to untreated cells, 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 microM 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.
- Subjects :
- Arsenites
Cell Survival
DNA damage
chemistry.chemical_element
Biology
medicine.disease_cause
Rats, Sprague-Dawley
chemistry.chemical_compound
Superoxide Dismutase-1
Settore BIO/10 - Biochimica
Genetics
medicine
Animals
Cell damage
Cells, Cultured
Arsenic
Arsenite
Superoxide Dismutase
General Medicine
medicine.disease
Molecular biology
Carcinogens, Environmental
Rats
Hsp70
Comet assay
Settore BIO/18 - Genetica
chemistry
Biochemistry
Apoptosis
Astrocytes
Comet Assay
inorganic arsenic, astrocytes, cell damage, DNA damage, PIPPin
Reactive Oxygen Species
Genotoxicity
DNA Damage
Subjects
Details
- ISSN :
- 1791244X and 11073756
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Medicine
- Accession number :
- edsair.doi.dedup.....c1540f207fd05385727c6dcf3eb02a1b