We have applied transcriptomic and proteomic techniques to identify changes in the RNA and the protein levels in the mouse cerebellum after chronic treatment with Δ9-tetrahydrocannabinol (THC). Among approximately 14,000 transcripts in a mouse cDNA microarray library, we found 11 genes with altered expression. RasGRF1, a neuron-specific Ras guanine nucleotide exchange factor, showed a reduction both at the RNA and protein levels with a specific decrease of the protein pool associated to cell membranes. In addition, proteomic analysis on cerebellum obtained from chronically THC-treated mice detected quantitative changes of additional 27 spots, mostly in the membranous fraction. We found enrichment of alpha (Gαo, Gαq) and beta subunits (β4/β2 and β5) of guanine nucleotide-binding proteins and of two calcium-binding proteins, calretinin and hippocalcin-like protein-1. In addition, we also detected a significant increase in the membrane fraction of proteins involved in exo-endocytosis such as septins, dynamin-1, and vesicle protein sorting 29. By western blotting, we confirmed increased membrane localization of calretinin and of dynamin-1 isoforms with higher isoelectric point, indicative for an underphosphorylated state of the molecule. In conclusion, our results indicate that chronic THC modulates the expression and subcellular localization of proteins implicated in Ras signaling, calcium-buffering potential, and trafficking. © 2008 Humana Press.

Colombo, G., Rusconi, F., Rubino, T., Cattaneo, A., Martegani, E., Parolaro, D., et al. (2009). Transcriptomic and proteomic analysis of mouse cerebellum reveals alterations in RasGRF1 expression following in vivo chronic treatment with delta 9-tetrahydrocannabinol. JOURNAL OF MOLECULAR NEUROSCIENCE, 37(2), 111-122 [10.1007/s12031-008-9114-2].

Transcriptomic and proteomic analysis of mouse cerebellum reveals alterations in RasGRF1 expression following in vivo chronic treatment with delta 9-tetrahydrocannabinol

MARTEGANI, ENZO;
2009

Abstract

We have applied transcriptomic and proteomic techniques to identify changes in the RNA and the protein levels in the mouse cerebellum after chronic treatment with Δ9-tetrahydrocannabinol (THC). Among approximately 14,000 transcripts in a mouse cDNA microarray library, we found 11 genes with altered expression. RasGRF1, a neuron-specific Ras guanine nucleotide exchange factor, showed a reduction both at the RNA and protein levels with a specific decrease of the protein pool associated to cell membranes. In addition, proteomic analysis on cerebellum obtained from chronically THC-treated mice detected quantitative changes of additional 27 spots, mostly in the membranous fraction. We found enrichment of alpha (Gαo, Gαq) and beta subunits (β4/β2 and β5) of guanine nucleotide-binding proteins and of two calcium-binding proteins, calretinin and hippocalcin-like protein-1. In addition, we also detected a significant increase in the membrane fraction of proteins involved in exo-endocytosis such as septins, dynamin-1, and vesicle protein sorting 29. By western blotting, we confirmed increased membrane localization of calretinin and of dynamin-1 isoforms with higher isoelectric point, indicative for an underphosphorylated state of the molecule. In conclusion, our results indicate that chronic THC modulates the expression and subcellular localization of proteins implicated in Ras signaling, calcium-buffering potential, and trafficking. © 2008 Humana Press.
Articolo in rivista - Articolo scientifico
Ras, CDC25, Affymetrix, cannabinoids
English
2009
37
2
111
122
none
Colombo, G., Rusconi, F., Rubino, T., Cattaneo, A., Martegani, E., Parolaro, D., et al. (2009). Transcriptomic and proteomic analysis of mouse cerebellum reveals alterations in RasGRF1 expression following in vivo chronic treatment with delta 9-tetrahydrocannabinol. JOURNAL OF MOLECULAR NEUROSCIENCE, 37(2), 111-122 [10.1007/s12031-008-9114-2].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/21168
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