TAILIEUCHUNG - Báo cáo khoa học: Changes in rat liver mitochondria with aging Lon protease-like activity and N e-carboxymethyllysine accumulation in the matrix

Aging is accompanied by a gradual deterioration of cell functions. Mitochondrial dysfunction and accumulation of protein damage have been proposed to contribute to this process. The present study was carried out to examine the effects of aging in mitochondrial matrix isolated from rat liver. The activity of Lon protease, an enzyme implicated in the degradation of abnormal matrix proteins, was meas-ured and the accumulation of oxidation and glycoxidation (N e -carboxymethyllysine, CML) products was monitored using immunochemical assays | Eur. J. Biochem. 270 2295-2302 2003 FEBS 2003 doi Changes in rat liver mitochondria with aging Lon protease-like activity and -carboxymethyllysine accumulation in the matrix Hilaire Bakala1 Evelvne Delaval1. Maud Hamelin1 Jeanne Bismuth1 Caroline Borot-Laloi1 Bruno Corman2 and Bertrand Friguet1 1Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement Universite Paris7-Denis Diderot Paris France 2Service de Biologic Cellulaire Commissariat à l Energie Atomique Saclay Gif-sur-Yvette France Aging is accompanied by a gradual deterioration of cell functions. Mitochondrial dysfunction and accumulation of protein damage have been proposed to contribute to this process. The present study was carried out to examine the effects of aging in mitochondrial matrix isolated from rat liver. The activity of Lon protease an enzyme implicated in the degradation of abnormal matrix proteins was measured and the accumulation of oxidation and glycoxidation N -carboxymethyllysine CML products was monitored using immunochemical assays. The function of isolated mitochondria was assessed by measuring respiratory chain activity. Mitochondria from aged 27 months rats exhibited the same rate of oxygen consumption as those from adult 10 months rats without any change in coupling efficiency. At the same time the ATP-stimulated Lon protease activity measured as fluorescent peptides released markedly decreased from 10-month-old rats FU-pg protein -h 1 to 27-month-old-rats FU-pg protein-1 h-1 . In parallel with this decrease in activity oxidized proteins accumulated in the matrix upon aging while the CML-modified protein content assessed by ELISA significantly increased by 52 from 10 months pmol CML-pg protein-1 to 27 months pmol CML-pg protein-1 . These results indicate that the accumulation of deleterious oxidized and carboxymethylated proteins in the matrix concomitant with loss of the Lon protease activity may .

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