TY - JOUR
T1 - Differential activation of mitogen-activated protein kinases by methyl methanesulfonate in the kidney of young and old rats
AU - Suh, Yousin
AU - Park, Sang Chul
N1 - Funding Information:
This work was supported by a research grant to Y. Suh (KRF-99-015-DP0287) from Korea Research Foundation. I thank Dr. Jan Vijg for support, critically reading the manuscript, and helpful discussions, and Kang-Ae Lee for technical assistance, and Bok-Ghee Han for providing animals.
PY - 2001/10/18
Y1 - 2001/10/18
N2 - Mitogen-activated protein kinases (MAPKs) play a critical role in the regulation of cell proliferation, differentiation and apoptosis. We evaluated MAPKs, extracellular signal-regulated kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAPKs in the kidney of young and old rats in response to a direct-acting alkylating agent, methyl methanesulfonate (MMS). It is shown that the basal activity of ERKs was strongly down-regulated in the kidney of old rats compared to their young counterparts without a significant difference in the basal expression of ERKs. Upon treatment with MMS, ERKs were deactivated about 5-fold (P < 0.05) in the kidney of young rats, whereas they were activated about 4-fold (P < 0.01) in old rats. Strikingly, expression of JNKs was not detected in old animals, whereas it was clearly present and strongly activated after MMS treatment in the kidney of young animals. The basal activity of p38 significantly increased in the kidney of old rats as compared to young animals, whereas no difference in the basal expression of p38 was detected. After treatment with MMS, p38 was activated in the kidney of both young and old rats, where activation was dramatically stronger than in young animals. Taken together, these results demonstrate age-specific MAPKs signaling pathways in the rat kidney. The implications in age-related changes in susceptibility of the kidney to MMS-induced carcinogenesis are discussed.
AB - Mitogen-activated protein kinases (MAPKs) play a critical role in the regulation of cell proliferation, differentiation and apoptosis. We evaluated MAPKs, extracellular signal-regulated kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAPKs in the kidney of young and old rats in response to a direct-acting alkylating agent, methyl methanesulfonate (MMS). It is shown that the basal activity of ERKs was strongly down-regulated in the kidney of old rats compared to their young counterparts without a significant difference in the basal expression of ERKs. Upon treatment with MMS, ERKs were deactivated about 5-fold (P < 0.05) in the kidney of young rats, whereas they were activated about 4-fold (P < 0.01) in old rats. Strikingly, expression of JNKs was not detected in old animals, whereas it was clearly present and strongly activated after MMS treatment in the kidney of young animals. The basal activity of p38 significantly increased in the kidney of old rats as compared to young animals, whereas no difference in the basal expression of p38 was detected. After treatment with MMS, p38 was activated in the kidney of both young and old rats, where activation was dramatically stronger than in young animals. Taken together, these results demonstrate age-specific MAPKs signaling pathways in the rat kidney. The implications in age-related changes in susceptibility of the kidney to MMS-induced carcinogenesis are discussed.
KW - Age-specific activation
KW - ERK
KW - JNK
KW - MAPK
KW - MMS
KW - p38
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U2 - 10.1016/S1383-5718(01)00207-8
DO - 10.1016/S1383-5718(01)00207-8
M3 - Article
C2 - 11525903
AN - SCOPUS:0035909498
SN - 1383-5718
VL - 497
SP - 11
EP - 18
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
IS - 1-2
ER -