TY - JOUR
T1 - 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
AU - Suh, Yousin
N1 - Funding Information:
This work was supported by a research grant to Yousin Suh (KRF-99-015-DP0287) from Korea Research Foundation. I thank Dr Sang Chul Park and Dr Jan Vijg for support, critically reading the manuscript, and helpful discussions, Kang-Ae Lee for technical assistance, and Dr Bok-Ghee Han for providing animals.
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - The stress-activated protein kinases (SAPKs), c-Jun NH2-terminal kinases (JNKs) 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 significant increase in the baseline expression levels of JNK isoforms was detected in 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 increased 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 young 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 increase 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 but 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 endogenous and environmentally induced genotoxic stress during aging are discussed.
AB - The stress-activated protein kinases (SAPKs), c-Jun NH2-terminal kinases (JNKs) 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 significant increase in the baseline expression levels of JNK isoforms was detected in 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 increased 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 young 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 increase 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 but 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 endogenous and environmentally induced genotoxic stress during aging are discussed.
KW - Alkylating agents
KW - DNA damage
KW - Methyl methanesulfonate (MMS)
KW - Organ-specific response
KW - Stress-activated protein kinases (SAPKs)
KW - c-Jun NH terminal kinase (JNK)
KW - p38
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U2 - 10.1016/S0047-6374(01)00301-3
DO - 10.1016/S0047-6374(01)00301-3
M3 - Article
C2 - 11557281
AN - SCOPUS:0034846004
SN - 0047-6374
VL - 122
SP - 1797
EP - 1811
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
IS - 15
ER -