Inhibition of protein kinase C promotes differentiation of neuroblastoma × glioma NG108-15 hybrid cells.

Eur J Neurosci 2011 Oct 21;34(7):1074-84. Epub 2011 Sep 21.

Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan.

Differentiation of neuroblastoma × glioma NG108-15 hybrid cells can be induced by different means, but the mechanisms involved are unclear. Our aim was to characterize the role of protein kinase C (PKC) in this process. The PKCs present in NG108-15 cells, i.e. PKCα, PKCδ, PKCε and PKCζ, were inhibited using a cocktail of Go6983 and Ro318220 or were downregulated by treatment with phorbol 12-myristate 13-acetate (PMA). In high-glucose Dulbecco's modified Eagle medium, neuritogenesis was induced by 24 h treatment with a cocktail of Go6983 and Ro318220 or by 48 h treatment with PMA, the latter process thus requiring a longer treatment. However, when cells treated with PMA for only 24 h were placed in extracellular standard salts solution, e.g. Locke's buffer, for 3 h, morphological and functional differentiation occurred, with rounding of the cell body, actin polymerization subjacent to the plasma membrane and an increase in voltage-sensitive Ca(2+) channel activity in the absence of cell death. This rapid differentiation was not due to autophagy, growth arrest or increased cyclic AMP response element binding protein phosphorylation, but coincided with combined activation of p38 mitogen-activated protein kinase (MAPK) and inhibition of extracellular signal-regulated kinase (ERK) and Akt, as confirmed by the effects of selective inhibitors. Furthermore, PKC activation blocked thapsigargin-induced neuritogenesis, whereas PKC downregulation did not. These results show that PKC downregulation promotes differentiation and this effect is accelerated by exposure to Locke's buffer. Although this experimental paradigm cannot be related to the in vivo situation and disease, it implies that combined inhibition of Akt and p44/p42 ERK and activation of p38 MAPK promotes differentiation.

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http://dx.doi.org/10.1111/j.1460-9568.2011.07835.xDOI Listing
October 2011
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References

(Supplied by CrossRef)
Monodansylcadaverine (MDC) is a specific in vivo marker for autophagic vacuoles
Biederbick et al.
Eur. J. Cell Biol. 1995
Induction of differentiation increases met5-enkephalin and leu5-enkephalin content in NG108-15 hybrid cells: an immunocytochemical and biochemical analysis
Braas et al.
J. Neurochem. 1983

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