Action ofl-acetylcarnitine on age-dependent modifications of mitochondrial membrane proteins from rat cerebellum

Abstract

Protein patterns of mitochondrial outer membrane, inner membrane, and matrix from non-synaptic (free) mitochondria from rat cerebellum at different ages (4, 8, 12, 16, 20, and 24 months) were analyzed by gel electrophoresis. Acute L-acetylcarnitine treatment was performed by a single i.p. injection (100 mg/kg body weight) of the substance 60 min before the sacrifice of the animals. Different age-dependent changes were obtained for the proteins of the three fractions. The amount of some protein subunits increased and/or decreased after drug treatment. In particular, protein composition of the inner mitochondrial membrane showed significant age-related modifications. This result probably indicates differences in protein synthesis and/or turnover rates in the various mitochondrial compartments during aging. Acute L-acetylcarnitine treatment caused: a high increase in the amount of one inner membrane protein with Mw 16 kDa, at all the ages studied; a decrease in the amount of many other inner membrane proteins; modifications of some matrix proteins. Our results show that in vivo administration of L-acetylcarnitine affects mainly the inner membrane protein composition of cerebellar mitochondria.

Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression

“…ALCAR administration alters mitochondrial inner membrane protein composition of rat cerebellum 25 and significantly increases glycerophosphocholine levels in 6-month-old rats but slightly decreases glycerophosphocholine levels in 24-month-old rats. 26 ALCAR also increases the membrane molecular dynamics of brain microsomes and liposomes produced from rat brain microsomal lipid extracts 27 and carnitine partially shares this effect with ALCAR.…”

“…94 However, ALCAR did not have any normalizing effect on catecholamine concentrations, tyrosine hydroxylase, neurofilament or glial fibrillary acid protein, suggesting the ALCAR protective action could be related to energy metabolism and not to effects on dopaminergic systems. Forloni et al 95 reported that ALCAR reduces the mortality in rat brain cell cultures after exposure to neurotoxic stimuli including NMDA and A␤ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) peptide and ALCAR can inhibit cell apoptosis and retard DNA fragmentation and nuclear condensation in a teratocarcinoma cell line in which apoptosis was induced by serum deprivation. 96 Although this last study was done in a non-brain tissue, it may indicate that ALCAR could have similar effects in CNS tissue.…”

Effects of Long-term Acetyl-L-carnitine Administration in Rats I. Increased Dopamine Output in Mesocorticolimbic Areas and Protection toward Acute Stress Exposure

“…ALCAR has a modulating influence on the structure, function and metabolism of cell membranes (Villa et al 1988;Aureli et al 1990;Arduini et al 1993;Butterfield and Rangachari 1993), and on energy metabolism (Aureli et al 1990;Rosenthal et al 1992;Blokland et al 1993;Liu et al 1993;Prickaerts et al 1995;Rao et al 1997). There is increasing evidence that abnormalities in fatty acid and membrane phospholipid metabolism play a part in a wide range of neurodevelopmental and psychiatric disorders (Richardson and Ross 2000;Bell et al 2000;Richardson and Puri 2000).…”

The effect of aging and acetyl‐L‐carnitine on the pyruvate transport andoxidation in rat heart mitochondria

“…Fax: (39) (80) 5443317. E-mail: g.paradies@biologia, uniba.it Abbreviation: ALCAR, acetyl-L-carnitine by acetyl-k-carnitine (ALCAR), a normal component of the rnitochondrial membrane [9][10][11][12]. We have recently reported that the activity of several anion carrier proteins such as the phosphate [13], ADP/ATP [14] and carnitine carriers [5] as well as that of cytochrome oxidase [14] is depressed in cardiac mitochondria from aged rats and that treatment of aged rats with ALCAR restored the activity of these membrane-bound proteins to the level of young control rats.…”