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Activation of Mitogen Activated Protein Kinase pathways during the death of PC12 cells is dependent on the state of differentiation

Activation of Mitogen Activated Protein Kinase pathways during the death of PC12 cells is dependent on the state of differentiation
Activation of Mitogen Activated Protein Kinase pathways during the death of PC12 cells is dependent on the state of differentiation
PC12 cells that are differentiated with NGF and cAMP become totally dependent on these factors for their survival, unlike those that are differentiated with NGF alone. We have asked whether the MAP Kinases, ERKs, JNKs and p38s play a role in the cell death induced by withdrawal of trophic factors on NGF- and NGF/cAMP-differentiated PC12 cells. By Western-blot analyses with antibodies directed against the activated forms of these kinases, we show that when the trophic factors were withdrawn, ERK phosphorylation was reduced to very low levels within 1 h in both cases. Changes in the other enzymes were observed only in the NGF/cAMP-differentiated cells, in which the JNK phosphorylation increased about 160% by 6 h and that of p38 increased linearly to at least 18-fold throughout the cell death process. The increases in p38 and JNK phosphorylation were implicated in the death of the cells, since the p38 inhibitor PD169316 and the JNK inhibitor SP600125 were protective. These results demonstrate that the state of differentiation of PC12 cells, a model for the differentiation of sympathetic neurons, determines their vulnerability to cell death by modifying the state of phosphorylation and the regulation of specific kinases implicated in signal transduction pathways that are responsible for the survival or the death of these cells.
cAMP, NGF, p38, ERK, JNK, MAPK, trophic factor withdrawal
0169-328x
52-60
Lambeng, N.
cc75cd38-e727-4e4a-9835-d99909b2ca13
Willaime-Morawek, S.
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Mariani, J.
d41a573a-a1ac-4c1b-b8d3-d97fad4756d1
Ruberg, M.
9312554b-7648-4e07-a567-02c17bffe2b8
Brugg, B.
47c3b9cc-b1ab-4a9c-addd-a100221e513a
Lambeng, N.
cc75cd38-e727-4e4a-9835-d99909b2ca13
Willaime-Morawek, S.
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Mariani, J.
d41a573a-a1ac-4c1b-b8d3-d97fad4756d1
Ruberg, M.
9312554b-7648-4e07-a567-02c17bffe2b8
Brugg, B.
47c3b9cc-b1ab-4a9c-addd-a100221e513a

Lambeng, N., Willaime-Morawek, S., Mariani, J., Ruberg, M. and Brugg, B. (2003) Activation of Mitogen Activated Protein Kinase pathways during the death of PC12 cells is dependent on the state of differentiation. Molecular Brain Research, 111 (1-2), 52-60. (doi:10.1016/S0169-328x(02)00669-1).

Record type: Article

Abstract

PC12 cells that are differentiated with NGF and cAMP become totally dependent on these factors for their survival, unlike those that are differentiated with NGF alone. We have asked whether the MAP Kinases, ERKs, JNKs and p38s play a role in the cell death induced by withdrawal of trophic factors on NGF- and NGF/cAMP-differentiated PC12 cells. By Western-blot analyses with antibodies directed against the activated forms of these kinases, we show that when the trophic factors were withdrawn, ERK phosphorylation was reduced to very low levels within 1 h in both cases. Changes in the other enzymes were observed only in the NGF/cAMP-differentiated cells, in which the JNK phosphorylation increased about 160% by 6 h and that of p38 increased linearly to at least 18-fold throughout the cell death process. The increases in p38 and JNK phosphorylation were implicated in the death of the cells, since the p38 inhibitor PD169316 and the JNK inhibitor SP600125 were protective. These results demonstrate that the state of differentiation of PC12 cells, a model for the differentiation of sympathetic neurons, determines their vulnerability to cell death by modifying the state of phosphorylation and the regulation of specific kinases implicated in signal transduction pathways that are responsible for the survival or the death of these cells.

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Published date: 17 March 2003
Keywords: cAMP, NGF, p38, ERK, JNK, MAPK, trophic factor withdrawal

Identifiers

Local EPrints ID: 66437
URI: http://eprints.soton.ac.uk/id/eprint/66437
ISSN: 0169-328x
PURE UUID: f52a27e6-d675-47b4-9041-f9bcce2ad9f3
ORCID for S. Willaime-Morawek: ORCID iD orcid.org/0000-0002-1121-6419

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Date deposited: 16 Jun 2009
Last modified: 14 Mar 2024 02:53

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Contributors

Author: N. Lambeng
Author: J. Mariani
Author: M. Ruberg
Author: B. Brugg

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