Cytoprotective Effect of Acetyl-l-Carnitine Evidenced by Analysis of Gene Expression in the Rat Brain

Mol Neurobiol (2009) 39:101106 DOI 10.1007/s12035-009-8056-1

Cytoprotective Effect of Acetyl-L-Carnitine Evidenced by Analysis of Gene Expression in the Rat Brain

Giovanna Traina & Giuseppe Federighi &

Marcello Brunelli & Rossana Scuri

Received: 26 November 2008 /Accepted: 22 January 2009 /Published online: 7 February 2009 # Humana Press Inc. 2009

Abstract Acetyl-L-carnitine (ALC), the acetyl ester of

L-carnitine, is a naturally occurring substance that when administered at supraphysiological concentrations is neuro-protective. ALC plays an essential role in intermediary and mitochondrial metabolism. It has also neurotrophic and antioxidant actions. ALC has demonstrated efficacy and high tolerability in the treatment of neuropathies of various etiologies, and it is a molecule of considerable interest for its clinical application in various neural disorders, such as Alzheimers disease and painful neuropathies, although little is known regarding the effects of ALC on gene expression. Suppression subtractive hybridization methodology was used for the generation of subtracted complementary DNA libraries and the subsequent identification of differentially expressed transcripts in the rat brain after a chronic ALC treatment. In the present paper, we provide evidences for the up-regulation of the expression of prostaglandin D2 synthase, brain-specific Na+-dependent inorganic phosphate transporter, and cytochrome b oxidase, bc1 complex induced in the rat brain by ALC. On the contrary, ALC treatment down-regulates the expression of the gene of ferritin-H. Altogether, these results suggest that ALC might play a cytoprotective role against various brain stressors.

Keywords Acetyl-L-carnitine . Rat . Brain .

Suppression subtractive hybridization . Cytoprotection

Introduction

Acetyl-L-carnitine (ALC) is the acetyl ester of the trimethylated amino acid L-carnitine (LA) that plays an essential role in energy production as shuttles of long-chain fatty acids between the cytosol and the mitochondria for subsequent oxidation [13]. Together with LA, ALC is involved in the control of mitochondrial acyl-CoA/CoA ratio and peroxisomal oxidation of fatty acids [4]. ALC exerts cytoprotective, antioxidant, and anti-apoptotic activity, and many studies have focused on the neurotrophic effects of ALC in the nervous system [5], since it is more widely used than its closer analog LA because it enters cells and crosses more efficiently the blood brain barrier [6]. In addition, ALC improves different aspects of the neuronal metabolism [710] and has wide neuromodulatory effects [4, 1113]. ALC is involved in cognitive functions and neuronal bioenergetics...