Interleukin-1beta-induced apoptosis through adenylyl cyclase and ERK1/2 inhibition in primary cultured thyroid cells.
(2006) Biochemical and Biophysical Research Communications — Vol. 339, n° 2, p. 469-476 (2006)
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Interleukin-1β-inducedapoptosisthroughadenylylcyclaseandERK1_2inhibitioninprimaryculturedthyroidcells2006.pdf
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- The programmed cell death plays a crucial role in the regulation of numerous physiological and pathological phenomena. In this study, we show that interleukin-1 beta (IL-1beta) induces an early production of endogenous ceramides via N-sphingomyelinase (N-Smase) as well as an inhibition of adenylyl cyclase activity in pig thyroid cells. This effect is followed by a down-regulation of the extracellular signal-regulated protein kinase (ERK1/2) phosphorylation, an activation of caspase-3, and ends by setting up the programmed cell death. The permeable exogenous C(2)-ceramide reproduces IL-1beta effects on: (i) inhibition of adenylyl cyclase activity, (ii) down-regulation of ERK1/2 phosphorylation, (iii) activation of caspase-3, and (iv) apoptosis in pig thyroid cells. Cell treatment with a PKA inhibitor down-regulates ERK1/2 phosphorylation. Furthermore, inhibition of ERK1/2 signaling pathway by U-0126 enhances caspase-3 activity and sets up programmed cell death. Both IL-1beta and exogenous C(2)-ceramide effects are reproduced by U-0126 so illustrating the implication of ERK1/2 down-regulation in both caspase-3 activation and apoptosis induction. Our study shows for the first time that endogenous ceramides are important second messengers in IL-1beta-induced apoptosis in pig thyroid cells through inhibition of adenylyl cyclase and ERK1/2 activities.
Citations
El Btaouri, H., Rath, G., Morjani, H., Schneider, C., Petitfrere, E., Antonicelli, F., & Martiny, L. (2006). Interleukin-1beta-induced apoptosis through adenylyl cyclase and ERK1/2 inhibition in primary cultured thyroid cells. Biochemical and Biophysical Research Communications, 339(2), 469-476. https://doi.org/10.1016/j.bbrc.2005.10.213 (Original work published 2006)