Age-related decline in S-adenosylmethionine and protein methyl esterification levels in bovine lenses

Abstract

The enzymatic methyl esterification of proteins, catalyzed by the enzyme S-adenosylmethionine: protein carboxyl-O-methyl transferase (PCMT), has been investigated in two age-related fractions of bovine lenses. The eukaryotic PCMT methyl esterifies peptides and proteins containing altered aspartyl residues, such as D-aspartyls and L-isoaspartyls, which can arise from the age-dependent deamidation of labile Asn residues. When intact bovine lenses were incubated in a cell culture medium under physiological conditions (pH 7.4, 37 degrees C), in the presence of L-(methyl-(14)C)methionine, the in vivo precursor of the methyl donor substrate S-adenosylmethionine (AdoMet), a significant decrease in the level of protein methyl esterification was observed in the oldest cell fraction compared to the youngest one; in contrast, the in vitro activity of PCMT does not change during cell aging. It has also been demonstrated that the cell aging in the lens is accompanied by a reduction of the AdoMet synthetase activity and, consequently, of the endogenous level of the methyl donor AdoMet. Furthermore, the activity of the enzyme S-adenosylhomocysteine (AdoHcy) hydrolase, which cleaves the methylation inhibitor AdoHcy, also appears dramatically reduced in the oldest cells, probably leading to an increase in the AdoHcy cellular level. Finally, the possible correlation between the decrease in the efficiency of the overall methyl esterification process during aging and the accumulation of aberrant forms of proteins observed in aged tissues is also discussed.