An increase in O -GlcNAcylation of Sp1 down-regulates the gene expression of pi class glutathione S -transferase in diabetic mice.

Autor:	Oliveri LM; Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, Universidad de, Buenos Aires, Argentina., Buzaleh AM; Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, Universidad de, Buenos Aires, Argentina.; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de, Buenos Aires, Argentina., Gerez EN; Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, Universidad de, Buenos Aires, Argentina.; Cátedra Bioquímica General Celular y Molecular, Facultad de Ciencias Médicas, Universidad Católica Argentina (UCA), Buenos Aires, Argentina.
Jazyk:	angličtina
Zdroj:	Biochemistry and biophysics reports [Biochem Biophys Rep] 2021 Jun 19; Vol. 27, pp. 101049. Date of Electronic Publication: 2021 Jun 19 (Print Publication: 2021).
DOI:	10.1016/j.bbrep.2021.101049
Abstrakt:	Oxidative stress is a key factor contributing to the development of diabetes complications. Glutathione S -transferases (GSTs) protect against products of oxidative stress by conjugating glutathione to electrophilic substrates, producing compounds that are generally less reactive and more soluble. The expression and activity of GSTs during diabetes have been extensively studied, but little is known about regulation mechanisms of Pi-class GST (GSTP). The aim of the present study was to evaluate how GSTP is regulated in a Streptozotocin (STZ)-induced murine diabetes model. GST activity and GSTP expression were determined in adult male mice diabetized with STZ. Specificity protein 1 (Sp1) expression and O-glycosylation, as well as the role of AP-1 members Jun and Fos in the regulation of GSTP expression, were also assessed. The results showed that GST total activity and GSTP mRNA and protein levels were decreased in the diabetic liver, and returned to normal values after insulin administration. The insulin-mimetic drug vanadate was also able to restore GST activity, but failed to recover GSTP mRNA/protein levels. In diabetic animals, O -glycosylated Sp1 levels were increased, whereas, in insulin-treated animals, glycosylation values were similar to those of controls. After vanadate administration, Sp1 expression levels and glycosylation were lower than those of controls. Our results suggest that hyperglycemia could lead to the observed increase in Sp1 O-glycosylation, which would, in turn, lead to a decrease in the expression of Sp1-dependent GSTP in the liver of diabetic mice. Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. (© 2021 The Authors. Published by Elsevier B.V.)
Databáze:	MEDLINE
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