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High Dosage Lithium Treatment Induces DNA Damage and p57Kip2 Decrease

Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(3), 1169;
Received: 15 December 2019 / Revised: 6 February 2020 / Accepted: 7 February 2020 / Published: 10 February 2020
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
Lithium salt is the first-line therapeutic option for bipolar disorder and has been proposed as a potential antitumoral drug. The effects of LiCl treatment were investigated in SH-SY5Y, a human neuroblastoma cell line and an in vitro model of dopaminergic neuronal differentiation. LiCl, at the dosage used in psychiatric treatment, does not affect cell proliferation, while at higher doses it delays the SH-SY5Y cell division cycle and for prolonged usage reduces cell viability. Moreover, the ion treatment affects DNA integrity as demonstrated by accumulation of p53 and γH2AX (the phosphorylated form of H2AX histone), two important markers of genome damage. p57Kip2, a CIP/Kip protein, is required for proper neuronal maturation and represents a main factor of response to stress including genotoxicity. We evaluated the effect of lithium on p57Kip2 levels. Unexpectedly, we found that lithium downregulates the level of p57Kip2 in a dose-dependent manner, mainly acting at the transcriptional level. A number of different approaches, mostly based on p57Kip2 content handling, confirmed that the CKI/Kip reduction plays a key role in the DNA damage activated by lithium and suggests the unanticipated view that p57Kip2 might be involved in DNA double-strand break responses. In conclusion, our study identified novel roles for p57Kip2 in the molecular mechanism of lithium at high concentration and, more in general, in the process of DNA repair. View Full-Text
Keywords: p57Kip2; LiCl; SH-SY5Y; oxidative stress; DNA damage; DNA damage response p57Kip2; LiCl; SH-SY5Y; oxidative stress; DNA damage; DNA damage response
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MDPI and ACS Style

Stampone, E.; Bencivenga, D.; Barone, C.; Aulitto, A.; Verace, F.; Della Ragione, F.; Borriello, A. High Dosage Lithium Treatment Induces DNA Damage and p57Kip2 Decrease. Int. J. Mol. Sci. 2020, 21, 1169.

AMA Style

Stampone E, Bencivenga D, Barone C, Aulitto A, Verace F, Della Ragione F, Borriello A. High Dosage Lithium Treatment Induces DNA Damage and p57Kip2 Decrease. International Journal of Molecular Sciences. 2020; 21(3):1169.

Chicago/Turabian Style

Stampone, Emanuela, Debora Bencivenga, Clementina Barone, Arianna Aulitto, Federica Verace, Fulvio Della Ragione, and Adriana Borriello. 2020. "High Dosage Lithium Treatment Induces DNA Damage and p57Kip2 Decrease" International Journal of Molecular Sciences 21, no. 3: 1169.

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