Diabetes and Pi Class Glutathione S-Transferase| Chapter 12 | New Innovations in Chemistry and Biochemistry Vol.7

 Chronic hyperglycemia is a symptom of diabetes mellitus, which is caused by insulin secretion and/or action abnormalities. Hyperglycemia causes oxidative stress by generating free radicals, which weakens the body's natural antioxidant defence mechanism. The development of diabetes complications is aided by the presence of oxidative stress. Glutathione S-transferases (GSTs) are a multigene family of enzymes that catalyse the conjugation of glutathione with electrophilic molecules, such as those formed during oxidative stress. One of the GST isoenzymes, Pi-class GST (GSTP), shows a strong affinity for tiny unsaturated aldehydes. Although much has been learned about the expression and activity of GSTs during diabetes, less is known about GSTP regulatory mechanisms. The transcription factors activator protein-1 (AP1) and Specificity protein 1 (SP1) have binding sites in the 5'-regulatory region of the mouse GSTP gene (Sp1). The goal of this work was to see how GSTP is regulated in a mouse diabetes model caused by streptozotocin (STZ). In mature male mice diabetized with STZ, GST activity and GSTP expression were measured. The involvement of AP-1 members Jun and Fos in the control of GSTP expression, as well as Sp1 expression and O-glycosylation, were all investigated. The findings revealed that in the diabetic liver, GST total activity, GSTP mRNA, and protein levels were reduced, but reverted to normal after insulin treatment. Vanadate, an insulin-mimetic medication, was likewise able to restore GSTs activity but not GSTP mRNA/protein levels. Both GSTs activity and GSTP mRNA were largely restored when the rats were given vitamin E. O-glycosylated Sp1 levels were higher in diabetic rats, whereas glycosylation levels in insulin-treated animals were equivalent to controls. Sp1 expression and glycosylation were lower after vanadate treatment than in controls. Our findings imply that hyperglycemia may cause an increase in Sp1 O-glycosylation, which would result in a decrease in the production of Sp1-dependent GSTP in diabetic mice's livers.

 

Author(s) Details:

Leda María Oliveri,
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Argentina.

Sandra Mora Milena,
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Argentina.

Ana María Buzaleh,
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Argentina and Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.

Esther Noemí Gerez,
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Argentina and Cátedra de Bioquímica General Celular y Molecular, Facultad de Ciencias Médicas, Universidad Católica Argentina (UCA), Buenos Aires, Argentina.

Please see the link here: https://stm.bookpi.org/NICB-V7/article/view/5928