Vol 47, No 4 (2009)
Original paper
Submitted: 2011-12-19
Published online: 2010-05-01
Cytoprotective effect of lithium against spontaneous and induced apoptosis of lymphoid cell line MOLT-4.
K Pietruczuk, A Jóźwik, K Ruckemann-Dziurdzińska, E Bryl, J M Witkowski
DOI: 10.2478/v10042-009-0118-8
·
Folia Histochem Cytobiol 2009;47(4):639-646.
Vol 47, No 4 (2009)
ORIGINAL PAPERS
Submitted: 2011-12-19
Published online: 2010-05-01
Abstract
Lithium (Li) is still useful in the treatment of bipolar disorder. Cellular mechanisms of Li action are not fully understood and include some cytoprotective properties. Data concerning Li effect on the apoptotic mechanisms in cells other than neurons are fragmentary and contradictory. We have investigated anti-apoptotic activity of Li in a lymphoid derived MOLT-4 cell line. Spontaneous and camptothecin-induced apoptosis was analyzed in cells treated with 0-20 mM Li carbonate. Early apoptosis was identified as significant mitochondrial depolarization (JC-1 staining). Later stages of apoptosis were estimated with annexin V binding and by the proportion of cells containing sub-G1 amounts of DNA (PI staining). We have observed a biphasic effect of Li on the proportion of spontaneously apoptotic cells;namely, low (therapeutic) concentrations of Li had a significant effect stabilizing the mitochondrial membrane polarization, while 10 and 20mM Li increased apoptosis. The latter could be seen both as mitochondrial depolarization as well as an increased proportion of sub-G1 cells, accompanied by reduced proportion of S phase cells. Li at concentrations above 2 mM had a significant, dose-dependent, anti-apoptotic effect on the cells undergoing camptothecin induced apoptosis. In conclusion, demonstrated cytoprotective effect of Li is at least partially related to stabilization of mitochondrial membrane potential and to the reduction of DNA damaging effects in proliferating cells; both may form part of the mechanism through which Li is useful in therapy of bipolar disorder, but may have more general consequences.
Abstract
Lithium (Li) is still useful in the treatment of bipolar disorder. Cellular mechanisms of Li action are not fully understood and include some cytoprotective properties. Data concerning Li effect on the apoptotic mechanisms in cells other than neurons are fragmentary and contradictory. We have investigated anti-apoptotic activity of Li in a lymphoid derived MOLT-4 cell line. Spontaneous and camptothecin-induced apoptosis was analyzed in cells treated with 0-20 mM Li carbonate. Early apoptosis was identified as significant mitochondrial depolarization (JC-1 staining). Later stages of apoptosis were estimated with annexin V binding and by the proportion of cells containing sub-G1 amounts of DNA (PI staining). We have observed a biphasic effect of Li on the proportion of spontaneously apoptotic cells;namely, low (therapeutic) concentrations of Li had a significant effect stabilizing the mitochondrial membrane polarization, while 10 and 20mM Li increased apoptosis. The latter could be seen both as mitochondrial depolarization as well as an increased proportion of sub-G1 cells, accompanied by reduced proportion of S phase cells. Li at concentrations above 2 mM had a significant, dose-dependent, anti-apoptotic effect on the cells undergoing camptothecin induced apoptosis. In conclusion, demonstrated cytoprotective effect of Li is at least partially related to stabilization of mitochondrial membrane potential and to the reduction of DNA damaging effects in proliferating cells; both may form part of the mechanism through which Li is useful in therapy of bipolar disorder, but may have more general consequences.
Title
Cytoprotective effect of lithium against spontaneous and induced apoptosis of lymphoid cell line MOLT-4.
Journal
Folia Histochemica et Cytobiologica
Issue
Vol 47, No 4 (2009)
Article type
Original paper
Pages
639-646
Published online
2010-05-01
Page views
1949
Article views/downloads
1623
DOI
10.2478/v10042-009-0118-8
Bibliographic record
Folia Histochem Cytobiol 2009;47(4):639-646.
Authors
K Pietruczuk
A Jóźwik
K Ruckemann-Dziurdzińska
E Bryl
J M Witkowski
About this article