PMID- 24563652 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20140224 LR - 20211021 IS - 1687-8876 (Print) IS - 1687-8884 (Electronic) IS - 1687-8876 (Linking) VI - 2014 DP - 2014 TI - Lithium improves survival of PC12 pheochromocytoma cells in high-density cultures and after exposure to toxic compounds. PG - 135908 LID - 10.1155/2014/135908 [doi] LID - 135908 AB - 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. FAU - Fabrizi, Cinzia AU - Fabrizi C AD - Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy. FAU - De Vito, Stefania AU - De Vito S AD - Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy. FAU - Somma, Francesca AU - Somma F AUID- ORCID: 0000-0003-1003-4610 AD - Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy. FAU - Pompili, Elena AU - Pompili E AD - Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy. FAU - Catizone, Angela AU - Catizone A AD - Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy. FAU - Leone, Stefano AU - Leone S AD - Department of Science, Roma Tre University, Rome, Italy. FAU - Lenzi, Paola AU - Lenzi P AD - Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy. FAU - Fornai, Francesco AU - Fornai F AD - Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy ; I.R.C.C.S. Neuromed, Pozzilli, Italy. FAU - Fumagalli, Lorenzo AU - Fumagalli L AD - Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, Via A. Borelli 50, 00161 Rome, Italy. LA - eng PT - Journal Article DEP - 20140120 PL - United States TA - Int J Cell Biol JT - International journal of cell biology JID - 101517861 PMC - PMC3915898 EDAT- 2014/02/25 06:00 MHDA- 2014/02/25 06:01 PMCR- 2014/01/20 CRDT- 2014/02/25 06:00 PHST- 2013/10/11 00:00 [received] PHST- 2013/11/20 00:00 [accepted] PHST- 2014/02/25 06:00 [entrez] PHST- 2014/02/25 06:00 [pubmed] PHST- 2014/02/25 06:01 [medline] PHST- 2014/01/20 00:00 [pmc-release] AID - 10.1155/2014/135908 [doi] PST - ppublish SO - Int J Cell Biol. 2014;2014:135908. doi: 10.1155/2014/135908. Epub 2014 Jan 20.