Differential activation of mitogen-activated protein kinases by methyl methanesulfonate in the kidney of young and old rats.
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.
Suh
Y
Y
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-Gu, 110-799, Seoul, South Korea. suhys@plaza1.snu.ac.kr
Park
S C
SC
D000375:Aging / Q000378:metabolism*; D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004249:DNA Damage; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology*; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
D000477:Alkylating Agents; D002273:Carcinogens; D008741:Methyl Methanesulfonate; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases