JNK1 is inactivated during thiamine deficiency-induced apoptosis in human neuroblastoma cells

Thiamine deficiency results in selective neuronal damage. A number of mecha nismss have been proposed to account for brain damage associated with thiam ine deficiency and to account for thr focal nature of the loss of neurons. One proposed mechanism is programmed cell death. We found efficient inducti on of apoptosis in human neuroblastoma cells when the cells were derived of thiamine. Although extensive mitochondrial damage was seen, the release of cytochrome c, was not the triggering mechanism for thiamine deficiency-ind uced apoptosis. Instead, the activity of the cJun amino terminal kinase Jnk 1 Ir ns lost, and this loss correlated temporally with induction of apoptos is. The loss was specific for Jnk1; Jnk2/3 activity remained unchanged. Los s of Jnk1 activity was not found in lymphoblasts, a cell type that did not undergo apoptosis when deprived of thiamine. These findings suggest that th iamine deficiency results in a cellular stress that brings about the loss o f Jnk1 activity and the loss of its function of protecting cells from progr ammed cell death. We postulate that focal sensitivity to thiamine deficienc y results, in part, from specific neuronal cell types being susceptible to the inactivation of Jnk1 in response to depletion of cellular thiamine. (C) Elsevier Science Inc. 2000. All rights reserved.