Early gene response in lithium chloride induced apoptosis

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Abstract
Depending on the cellular context, lithium chloride can lead to enhanced proliferation, cell cycle arrest or apoptosis in mammalian cells. Although substantial work has been made to elucidate the downstream events in the case of lithium chloride-induced cellular proliferation, the molecular response to lithium chloride treatment in the apoptotic scenario is largely undefined. We have used quadruplicate human cDNA arrays with 8000 targets to analyze the early gene response in cultures of human T/C28a cells that undergo apoptosis in response to 20 mM lithium chloride treatment. Incubation of cell cultures with 20 mM lithium chloride for five hours caused alterations in the steady-state mRNA levels of a large number of genes. RT-PCR and real-time RT-PCR confirmed the array results for ten of eleven selected targets. In addition to one protein primarily associated with apoptosis, genes identified as differentially expressed based on microarray data mainly encode proteins involved in basic cellular functions such as signaling, cell cycle control and growth, cell-cell interaction, solute transport and transcription control. We present a list of 50 genes that were differentially expressed in response to lithium chloride treatment and which may represent a reference for further studies to define the pathways governing the apoptotic response to lithium chloride.