Transcriptional Analysis of Apoptotic Cerebellar Granule Neurons Following Rescue by Gastric Inhibitory Polypeptide

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.

Neuroprotective effects of glucose-dependent insulinotropic polypeptide in Alzheimer’s disease

“…The role of GIP in progenitor cell proliferation and neurogenesis GIP is a neurotrophic factor that can inhibit apoptosis of cerebellar granule cells (Maino et al, 2014). Activation of (Kim et al, 2008), cAMP/Akt/PKB (Kim et al, 2005b) and MAPK , and other signaling pathways.…”

Are obese rats influenced by GLP1 and IR through aerobic exercise? A case study

“…On the one hand, it directly increases insulin gene expression and its synthesis through receptors on pancreas cells (28,41). On the other hand, it increases insulin secretion through direct effect on its own receptors on pancreaticβ cells (20,26) and also indirectly through hepatic portal vein and vagus nerve system (7,12).…”

Drug target identification at the crossroad of neuronal apoptosis and survival

“…As mentioned above, transcriptional analysis of CGNs unveiled a large number of genes and pathways that are commonly deregulated during apoptosis and its rescue by Igf1 and Pacap [11]. Several of these genes encode known drug targets, which include ligands, G-protein-coupled receptors, ion channels, enzymes.…”

“…Our most recent studies, in particular, were the first to extend the analysis to survival and led to the identification of key drug targets deregulated in both apoptosis and growth factor rescue [11,15,26]. The following paragraphs will describe how this kind of approach was first utilized to characterize the transcriptional program at the intersection of apoptosis and survival of CGNs and to identify new potential drug targets.…”

“…Neurotrophic factors have been identified as the key factors in antagonizing neuronal apoptosis and promoting life signals in neuronal cells [10,11]. Delivery to the brain of these peptide molecules, however, is normally hindered by the blood-brain barrier (BBB), which limits the therapeutic utility of their exogenous administration [12].…”