GSH role on platelet-derived growth factor receptor tyrosine phosphorylation induced by H2O2.
This study, conducted on NIH3T3 cells, demonstrates that GSH depletion obtained by buthionine sulfoximine (BSO) treatment does not affect platelet-derived growth-factor receptor (PDGFr) autophosphorylation or cell protein phosphorylation induced by exogenous addition of H2O2, while it does decrease tyrosine phosphorylation obtained by PDGF stimulation. This last effect seems due to the lack of H2O2 generation; for the first time a relation between intracellular GSH content and H2O2 production induced by PDGF has been demonstrated. Therefore, changes of GSH levels can affect the early events of the PDGFr signal pathways by redox regulation. It has also demonstrated that in NIH3T3 cells, H2O2 can directly activate tyrosine phosphorylation by a reversible effect with the involvement of SH-group. This H2O2 effect is increased by vanadate and by GSH depleting agent, diethylmaleate, which unlike BSO is able to produce H2O2 as the current study shows.
Iantomasi
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T
Department of Biochemical Sciences, University of Firenze, viale Morgagni 50, 50134, Firenze, Italy.
Favilli
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F
Catarzi
S
S
Vincenzini
M T
MT
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000187:drug effects / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D008298:Maleates; D014638:Vanadates; D014443:Tyrosine; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D017479:Receptors, Platelet-Derived Growth Factor; D017027:Protein Tyrosine Phosphatases; C014476:diethyl maleate; D005978:Glutathione