title: Identification of differentially expressed genes induced in the rat brain by acetyl-L-carnitine as evidenced by suppression subtractive hybridisation.
abstract: Acetyl-L-carnitine (ALC) is a molecule widely present in the central nervous system (CNS) formed by the reversible acetylation of carnitine. It acts by stimulating energy metabolism. Reported neurobiological effects of this substance include modulation of brain energy and phospholipid metabolism; cellular macromolecules (including neurotrophic factors and neurohormones); synaptic transmission of multiple neurotransmitters. ALC is of considerable interest for its clinical application in Alzheimer's disease and in the treatment of painful neuropathies. There are experimental data that it affects attention and antagonizes deterioration of ability to learn, improving long-term memory. Moreover, ALC influences nonassociative learning of sensitization type in Hirudo medicinalis. These findings are suggesting that ALC might exert its effects by means of new protein synthesis. ALC or saline solution was injected intraperitoneally each day for 21 days in rats. Poly(A)+ RNAs were isolated from control and treated rat brain. Suppression subtractive hybridisation (SSH) method was applied for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after treatments. The technique generates an equalized representation of differentially expressed genes irrespective of their relative abundance, and it is based on the construction of forward and reverse cDNA libraries that allow the identification of the genes that are regulated or switched off/on after ALC treatment. We identified two modulated genes, the isoform gamma of 14-3-3 protein and a precursor of ATP synthase lipid-binding protein, and one gene switched on by the treatment, the heat shock protein hsp72.
authors.affiliation: Dipartimento di Fisiologia e Biochimica G. Moruzzi, Università di Pisa, Via S. Zeno, 31, 56127 Pisa, Italy. gtraina@dfb.unipi.it
authors.forename: Giovanna
authors.initials: G
authors.lastname: Traina
authors.forename: Simona
authors.initials: S
authors.lastname: Valleggi
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Bernardi
authors.forename: Milena
authors.initials: M
authors.lastname: Rizzo
authors.forename: Menotti
authors.initials: M
authors.lastname: Calvani
authors.forename: Raffaella
authors.initials: R
authors.lastname: Nicolai
authors.forename: Luigi
authors.initials: L
authors.lastname: Mosconi
authors.forename: Mauro
authors.initials: M
authors.lastname: Durante
authors.forename: Marcello
authors.initials: M
authors.lastname: Brunelli
mesh_terms: D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000235:genetics; D000108:Acetylcarnitine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D015723:Gene Library; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000096:biosynthesis / Q000235:genetics; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009693:Nucleic Acid Hybridization / Q000379:methods; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D048948:14-3-3 Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000108:Acetylcarnitine; D025261:Mitochondrial Proton-Translocating ATPases