Transcriptional analysis of apoptotic cerebellar granule neurons following rescue by gastric inhibitory polypeptide.
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.
Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Via Paolo Gaifami 18, 95126 Catania, Italy. barbara.maino@functional-genomics.it.
Barbara
B
Maino
European Brain Research Institute, Via del Fosso di Fiorano 64, 00143 Roma, Italy. mariateresa.ciotti@cnr.it.
Maria Teresa
MT
Ciotti
European Brain Research Institute, Via del Fosso di Fiorano 64, 00143 Roma, Italy. p.calissano@ebri.it.
Pietro
P
Calissano
Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Via Paolo Gaifami 18, 95126 Catania, Italy. sebastiano.cavallaro@cnr.it.
Sebastiano
S
Cavallaro
D000818:Animals; D000975:Antioxidants; D017209:Apoptosis / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002531:Cerebellum / Q000166:cytology*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D020869:Gene Expression Profiling; D009474:Neurons / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014158:Transcription, Genetic; D054875:Ubiquitination / Q000235:genetics
D000975:Antioxidants; D005749:Gastric Inhibitory Polypeptide