Differential activation of mitogen-activated protein kinases by methyl methanesulfonate in the kidney of young and old rats

Yousin Suh, Sang Chul Park

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11-18
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume497
Issue number1-2
DOIs
StatePublished - Oct 18 2001
Externally publishedYes

Fingerprint

Methyl Methanesulfonate
Mitogen-Activated Protein Kinases
Kidney
Extracellular Signal-Regulated MAP Kinases
JNK Mitogen-Activated Protein Kinases
Alkylating Agents
p38 Mitogen-Activated Protein Kinases
Cell Differentiation
Carcinogenesis
Cell Proliferation
Apoptosis

Keywords

  • Age-specific activation
  • ERK
  • JNK
  • MAPK
  • MMS
  • p38

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

Cite this

Differential activation of mitogen-activated protein kinases by methyl methanesulfonate in the kidney of young and old rats. / Suh, Yousin; Park, Sang Chul.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 497, No. 1-2, 18.10.2001, p. 11-18.

Research output: Contribution to journalArticle

@article{5eea800189a24bebb074cf9e69c90409,
title = "Differential activation of mitogen-activated protein kinases by methyl methanesulfonate in the kidney of young and old rats",
abstract = "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.",
keywords = "Age-specific activation, ERK, JNK, MAPK, MMS, p38",
author = "Yousin Suh and Park, {Sang Chul}",
year = "2001",
month = "10",
day = "18",
doi = "10.1016/S1383-5718(01)00207-8",
language = "English (US)",
volume = "497",
pages = "11--18",
journal = "Mutation Research - Genetic Toxicology and Environmental Mutagenesis",
issn = "1383-5718",
publisher = "Elsevier",
number = "1-2",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=0035909498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035909498&partnerID=8YFLogxK

U2 - 10.1016/S1383-5718(01)00207-8

DO - 10.1016/S1383-5718(01)00207-8

M3 - Article

C2 - 11525903

AN - SCOPUS:0035909498

VL - 497

SP - 11

EP - 18

JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

SN - 1383-5718

IS - 1-2

ER -