Selective expression of JNK isoforms and stress-specific JNK activity in different neural cell lines

The function of c-Jun N-terminal kinases (JNKs) in the nervous system is po orly understood and the majority of the data has been gained in neuronal an d non-neuronal cell lines. Thus, it is not clear to which extent the expres sion pattern and the degree of activation of the three JNK isoforms in diff erent cell Lines are representative for their activation in the adult brain . in the present study, the expression of JNK isoforms and the activity of JNK1 were determined following UV irradiation and exposure to H2O2 and TNF alpha in three neural cell lines, rat PC12, murine Neuro2A and human SHSY5Y . These cell lines differ in their expression of JNK isoforms: PC12 cells e xpress JNK1 and JNK2, whereas Neuro2A and SHSY5Y cells displays the express ion of JNK1. JNK2 and JNK3. JNK3 was not inducible following stress and dif ferentiation in PC12 cells. The stimulation paradigms evoked different degr ee of cell death: UV irradiation resulted in death of around 50% in all thr ee cell lines; exposure to 200 mu M H2O2 for 6 h resulted in the death of 4 3% Neuro2A cells and 31% PC12 cells, SHSY5Y cells are less sensitive to H2O 2 since only 5 mM H2O2 killed 59% of SHSY5Y cells after 6 h. Exposure to 50 ng/ml TNF alpha did not induce cell death in SHSY5Y, Neuro2A and naive PC1 2 cells. Although differentiated PC12 cells exhibit a similar activation of JNK1 compared to naive PC12 cells after exposure to TNF alpha. 42% of diff erentiated PC12 cells died after 24 h. H2O2 that evoked only a moderate JNK 1 activity in Neuro2A and PC12 cells induced only a moderate cell death. In contrast, SHSY5Y cells exhibit a much stronger JNK1 activation accompanied with a higher degree in cell death after exposure to H2O2. JNK1 activity i nduced by UV irradiation, however, could not be correlated with the extend of cell death. These. data clearly demonstrate that expression and activati on of JNK depends on the neuronal cell type and the applied stress paradigm s, and that JNK activity is not simply linked to cell death. (C) 2000 Elsev ier Science B.V. All rights reserved.