The role of H2O2 in the platelet-derived growth factor-induced transcription of the gamma-glutamylcysteine synthetase heavy subunit.
Cell Mol Life Sci
; 59(8): 1388-94, 2002 Aug.
Article
em En
| MEDLINE
| ID: mdl-12363041
ABSTRACT
This study demonstrates that platelet-derived growth factor (PDGF) increases transcription of the gamma-glutamylcysteine synthetase (GCS) heavy subunit (GCS-HS) in NIH 3T3 fibroblasts via H2O2 and activation of protein kinase C (PKC). The data obtained using catalase, H2O2, phorbol-12-myristate 13-acetate (PMA) or a specific inhibitor of PKC demonstrate the possibility of a PDGF up-regulation pathway of GCS synthesis. Moreover, since PDGF mitogenic activity takes place through PKC activation and sphingosine-1-phosphate (S1P) production, the involvement of sphingosine kinase activity in the PDGF effect was also investigated. No clear direct relationship emerged between S1P production and any PDGF- or H2O2-induced increase in the GCS-HS mRNA level. However, for the first time, in S1P-stimulated NIH 3T3 cells, increased levels of GCS-HS mRNA were shown to be related to increases in the reduced glutathione synthesis rate similar to those obtained after PMA and PDGF stimulation.
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Base de dados:
MEDLINE
Assunto principal:
Esfingosina
/
Fator de Crescimento Derivado de Plaquetas
/
Lisofosfolipídeos
/
Glutamato-Cisteína Ligase
/
Peróxido de Hidrogênio
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article