Age-specific changes in expression, activity, and activation of the c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinases by methyl methanesulfonate in rats

The stress-activated protein kinases (SAPKs), c-Jun NH2-terminal kinases (J NKs) and p38 mitogen-activated protein kinases, were evaluated in the liver and brain of young and old rats in response to a direct-acting alkylating agent, methyl methanesulfonate (MMS). A slight but statistically significan t increase in the baseline expression levels of JNK isoforms was detected i n both the liver and brain of old as compared with young rats. In the liver of both young and old rats, no basal activities of JNKs were detected. In the brain, JNK activities were constitutively high and significantly increa sed in old rats compared with their young counterparts. Upon MMS treatment, JNKs were strongly activated in the liver, but not in the brain, of both y oung and old animals. The basal activity of p38 significantly increased in both the liver and brain of old rats as compared with young rats. An increa se in the basal expression of p38 was detected in the brain but not in the liver of old rats. Upon treatment with MMS, p38 was activated in the liver of both young and old rats. In the brain, p38 was only activated in young b ut not in old rats. Taken together, these results demonstrate age-specific as well as organ-specific SAPKs signaling pathways in the rat in vivo. The possible implications of these findings in terms of resistance to endogenou s, and environmentally induced genotoxic stress during aging are discussed. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.