RT Journal Article
T1 Low concentrations of nitric oxide delay the differentiation of embryonic stem cells and promote their survival.
A1 Tejedo, J R
A1 Tapia-Limonchi, R
A1 Mora-Castilla, S
A1 Cahuana, G M
A1 Hmadcha, A
A1 Martin, F
A1 Bedoya, F J
A1 Soria, B
K1 Embryonic stem cell
K1 Leukemia Inhibitory Factor
K1 Differentiation
K1 Self-renewal
K1 Nitric Oxide
K1 Células madre embrionarias
K1 Factor Inhibidor de Leucemia
K1 Diferenciación celular
K1 Óxido Nítrico
AB Nitric oxide (NO) is an intracellular messenger in several cell systems, but its contribution to embryonic stem cell (ESC) biology has not been characterized. Exposure of ESCs to low concentrations (2-20 μM) of the NO donor diethylenetriamine NO adduct confers protection from apoptosis elicited by leukaemia inhibitory factor (LIF) withdrawal. NO blocked caspase 3 activation, PARP degradation, downregulation of the pro-apoptotic genes Casp7, Casp9, Bax and Bak1 and upregulation of the anti-apoptotic genes Bcl-2 111, Bcl-2 and Birc6. These effects were also observed in cells overexpressing eNOS. Exposure of LIF-deprived mESCs to low NO prevented the loss of expression of self-renewal genes (Oct4, Nanog and Sox2) and the SSEA marker. Moreover, NO blocked the differentiation process promoted by the absence of LIF and bFGF in mouse and human ESCs. NO treatment decreased the expression of differentiation markers, such as Brachyury, Gata6 and Gata4. Constitutive overexpression of eNOS in cells exposed to LIF deprivation maintained the expression of self-renewal markers, whereas the differentiation genes were repressed. These effects were reversed by addition of the NOS inhibitor L-NMMA. Altogether, the data suggest that low NO has a role in the regulation of ESC differentiation by delaying the entry into differentiation, arresting the loss of self-renewal markers and promoting cell survival by inhibiting apoptosis.
PB Nature Publishing Group
YR 2010
FD 2010-10-07
LK http://hdl.handle.net/10668/2255
UL http://hdl.handle.net/10668/2255
LA en
NO Tejedo JR, Tapia-Limonchi R, Mora-Castilla S, Cahuana GM, Hmadcha A, Martin F, et al. Low concentrations of nitric oxide delay the differentiation of embryonic stem cells and promote their survival. Cell Death Dis; 1:e80
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 6, 2025