Acetyl-l-carnitine up-regulates expression of voltage-dependent anion channel in the rat brain

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Abstract

Acetyl-l-carnitine (ALC) exerts unique neuroprotective, neuromodulatory, and neurotrophic properties, which play an important role in counteracting various pathological processes, and have antioxidative properties, protecting cells against lipid peroxidation. In this study, suppression subtractive hybridization (SSH) method was applied for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after treatment of rats with ALC. 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 after ALC treatment. In the present paper, we report the identification of the gene of mitochondrial voltage-dependent anion channel (VDAC) protein which is positively modulated by the ALC treatment. VDAC is a small pore-forming protein of the mitochondrial outer membrane. It represents an interesting tool for Ca2+ homeostasis, and it plays a central role in apoptosis. In addition, VDAC seems to have a relevant role in the synaptic plasticity.

Section snippets

Animals

Fifty-day-old male Wistar rats bred from the same litter, housed at a temperature of 22 °C, were intraperitoneally injected daily for 21 days with ALC (100 mg/kg body weight Sigma-Tau Laboratories, Pomezia, Italy, experimental group) or saline (control group), as described in a previous paper (Traina et al., 2004). The investigation has been conducted in conformity with the principles of the Declaration of Helsinky.

Subtracted cDNA library construction

Total RNA was isolated from rat brains (except cerebellum and spinal cord) of four

Results

The aim of this study was to single out genes that are differentially expressed in brains of young rats after 21 days ALC treatments. We have chosen to build the cDNA libraries from the whole brain of young healthy rats. To identify genes whose expressions were induced in response to ALC treatment in rat CNS, we used PCR-based suppression subtractive hybridization (Traina et al., 2004). In this paper, we report a finding that might be considered of particular relevance for the identification of

Discussion

The present study has singled out the influence of ALC treatment on genes expressed at mitochondrial level, already in part described in our previous paper (Traina et al., 2004). This is the first evidence reporting a modulation of expression of VDAC1 gene after ALC treatment in the rat brain. ALC seems to exert a pivotal role in the mechanisms which, at the level of mitochondrion, transfer the produced energy to the cellular membrane where they modulate the electrogenic pump subserving the

Acknowledgement

The authors thank Sigma-Tau Laboratories, Pomezia, Roma, for providing us with acetyl-l-carnitine and for supporting the work.

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