Abstract
Apoptosis triggered by exogenous or endogenous stimuli is a crucial phenomenon to determine the fate of neurons, both in physiological and in pathological conditions. Our previous study established that gastric inhibitory polypeptide (Gip) is a neurotrophic factor capable of preventing apoptosis of cerebellar granule neurons (CGNs), during its pre-commitment phase. In the present study, we conducted whole-genome expression profiling to obtain a comprehensive view of the transcriptional program underlying the rescue effect of Gip in CGNs. By using DNA microarray technology, we identified 65 genes, we named survival related genes, whose expression is significantly de-regulated following Gip treatment. The expression levels of six transcripts were confirmed by real-time quantitative polymerase chain reaction. The proteins encoded by the survival related genes are functionally grouped in the following categories: signal transduction, transcription, cell cycle, chromatin remodeling, cell death, antioxidant activity, ubiquitination, metabolism and cytoskeletal organization. Our data outline that Gip supports CGNs rescue via a molecular framework, orchestrated by a wide spectrum of gene actors, which propagate survival signals and support neuronal viability.
Highlights
Neuronal apoptosis represents a distinctive mode of programmed cell death that is characterized by an intrinsic suicide program, by which a neuron orchestrates its own destruction
We have recently showed that gastric inhibitory polypeptide (Gip) exerts a potent anti-apoptotic effect in cultured cerebellar granule neurons (CGNs) [16]
Two genes encoding proteins involved in chromatin remodelling are up-regulated by Gip during rescue of CGNs apoptosis: Chromodomain protein Y-like 2 (Cdyl2) and TEN1 CST complex subunit (Ten1)
Summary
Neuronal apoptosis represents a distinctive mode of programmed cell death that is characterized by an intrinsic suicide program, by which a neuron orchestrates its own destruction. Primary cultures of CGNs have been extensively utilized to examine the signal transduction mechanisms underlying neuronal apoptosis [11,12,13]. In this in vitro paradigm, CGNs undergo rapid apoptotic cell death within h after removal of serum and lowering of extracellular potassium from to 5 mM [8]. Apoptosis requires transcription and protein synthesis and becomes irreversible during the first six hours following induction Before this “commitment point”, CGNs can be rescued by the activation of specific signal transduction pathways or by the treatment with specific neurotrophic factors [8,14,15,16].
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