GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:16155909
| Citation |
Li, M, Liu, RM, Timblin, CR, Meyer, SG, Mossman, BT and Fukagawa, NK (2006) Age affects ERK1/2 and NRF2 signaling in the regulation of GCLC expression. J. Cell. Physiol. 206:518-25 |
|---|---|
| Abstract |
We previously reported that activator protein-1 (AP-1) DNA binding activity was increased in vascular smooth muscle cells (VSMC) from old rats when exposed to high glucose or tumor necrosis factor (TNF-alpha) (Li et al., 2003. J Cell Physiol 197:418-425). We have now examined the relationship between the age-dependent activation of the ERK1/2-AP-1 pathway and modulation of constitutive gene expression of the catalytic subunit of glutamate-cysteine ligase (GCLC) in response to high glucose and TNF-alpha. GCLC mRNA levels were higher in VSMC from old rats compared to young, a pattern consistent with its protein levels. To determine whether age-related activation of ERK1/2-AP-1 signaling is responsible for the up-regulation of GCLC, the MEK inhibitors, PD98059 and U0126, were used to block ERK1/2 in VSMC from old rats. An increase in GCLC with inhibitors was observed, diminishing the likelihood of ERK1/2-AP-1 activation as the up-regulating signal for GCLC. However, the transcription factor Nrf2 was higher in nuclei and accompanied by increased Nrf2-ARE binding in VSMC from old rats. Furthermore, MEK inhibitors increased nuclear Nrf2 and Nrf2/ARE binding. These data suggest opposing effects of Nrf2 and ERK1/2 signaling in the modulation of GCLC expression in old animals. |
| Links |
PubMed Online version:10.1002/jcp.20496 |
| Keywords |
Age Factors; Aging; Animals; Catalytic Domain; Cells, Cultured; Dose-Response Relationship, Drug; Glucose/pharmacology; Glutamate-Cysteine Ligase/metabolism; Glutathione/metabolism; MAP Kinase Kinase Kinases; Male; Mitogen-Activated Protein Kinase 3/metabolism; Muscle, Smooth, Vascular/cytology; Muscle, Smooth, Vascular/metabolism; NF-E2-Related Factor 2/metabolism; Proto-Oncogene Proteins c-fos/metabolism; Rats; Rats, Inbred F344; Signal Transduction; Time Factors; Tumor Necrosis Factor-alpha/pharmacology; Up-Regulation |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0007568: aging |
ECO:0000270: expression pattern evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
Notes
See also
References
See Help:References for how to manage references in GONUTS.
