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International Journal of Cell Biology
Volume 2014, Article ID 135908, 7 pages
Research Article

Lithium Improves Survival of PC12 Pheochromocytoma Cells in High-Density Cultures and after Exposure to Toxic Compounds

1Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy
2Department of Science, Roma Tre University, Rome, Italy
3Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy
4I.R.C.C.S. Neuromed, Pozzilli, Italy

Received 11 October 2013; Accepted 20 November 2013; Published 20 January 2014

Academic Editor: Claudia Giampietri

Copyright © 2014 Cinzia Fabrizi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Autophagy is an evolutionary conserved mechanism that allows for the degradation of long-lived proteins and entire organelles which are driven to lysosomes for digestion. Different kinds of stressful conditions such as starvation are able to induce autophagy. Lithium and rapamycin are potent autophagy inducers with different molecular targets. Lithium stimulates autophagy by decreasing the intracellular myo-inositol-1,4,5-triphosphate levels, while rapamycin acts through the inhibition of the mammalian target of rapamycin (mTOR). The correlation between autophagy and cell death is still a matter of debate especially in transformed cells. In fact, the execution of autophagy can protect cells from death by promptly removing damaged organelles such as mitochondria. Nevertheless, an excessive use of the autophagic machinery can drive cells to death via a sort of self-cannibalism. Our data show that lithium (used within its therapeutic window) stimulates the overgrowth of the rat Pheochromocytoma cell line PC12. Besides, lithium and rapamycin protect PC12 cells from toxic compounds such as thapsigargin and trimethyltin. Taken together these data indicate that pharmacological activation of autophagy allows for the survival of Pheochromocytoma cells in stressful conditions such as high-density cultures and exposure to toxins.