Changes of polyamine metabolism and autophagy in aging heart and effect of exogenous spermidine on autophagy in aged rat heart / 中国药理学通报

ABSTRACT

Aim To discuss the changes of polyamine metabolism and autophagy in aging rat heart and the effect of exogenous spermidine on autophay in aged rat heart. Methods Western blot assay was used to detect the expressions of ODC and SSAT-rate-limiting enzyme of polyamine anabolism and catabolism as well as the expression of autophagy-relevant protein LC3?/? and p62 in cardiac tissues from male Wistar rats aged 3, 6, 12 and 24 months, and the expressions of p16, LC3?/?, ATG5 and ATG7 protein were detected in cardiac tissues in rats aged 3 months, 24 months and 24 months with spermidine administrtion, respectively. The myocardial autophagosome formation was observed by transmission electron microscope. In addition, cell cross-sectional area, cell apoptosis rate and generation of ROS were evaluated. Results With heart aging in rats, ODC expression and LC3?/? ratio were degraded, and SSAT and p62 protein expression upgraded. In rats aged 24 months, myocardium showed increased p16 expression, cell cross-sectional area, cell apoptosis and ROS generation, while cell autophagosome formation decreased, p62 expression increased, the expression of LC3?/?, ATG5 and ATG7 all declined. Spermidine intervention obviously inhibited myocardial changes induced by aging, showing decrease in cell cross-sectional area, apoptosis, ROS generation and p62 expression, and increase in LC3?/?, ATG5 and ATG7 expression. Conclusions With heart aging in rats, polyamine anabolism is degraded, catabolism is upgraded, and cell autophagy declined. Exogenous spermidine might delay aging through inducing autophagy of cardiomyocytes.