Work

Regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type I

Year: 2025

Type: article

Abstract: Diabetes produces changes on cellular hemeprotein metabolism. The last enzyme of heme biosynthetic pathway is ferrochelatase (FECH), an enzyme that catalyzes the insertion of ferrous ion into protoporphyrin IX to produce heme. The aim of this work was to investigate whether FECH expression can be other key point in the regulation of heme biosynthesis in diabetic animals. Mice were rendered diabetic with streptozotocin (STZ, 170 mg/kg body weight i.p. for 15 days). Liver FECH protein and mRNA levels were evaluated by Western blot and Northern blot respectively. Vanadate was used as a hypoglycemic agent. The levels of the transcription factor Sp1 bound to the FECH promoter were assessed by chromatin immunoprecipitation (ChIP). Hyperglycemia caused an increase in FECH mRNA levels but no changes in FECH protein expression. ChIP analysis revealed that the increase in FECH mRNA levels was due to enhanced Sp1 binding to the FECH promoter in diabetic animals, which was reduced by vanadate administration. In diabetic animals, enhanced binding of Sp1 to the FECH promoter may be responsible for the increase in FECH mRNA levels. However, this increase was not reflected in the amount of FECH protein, which would confirm that FECH could be another control point in heme synthesis. • During diabetes, changes occur at the transcriptional levels of FECH mRNA. • Hyperglycemia leads to an increase in the amount of Sp1 bound to FECH promoter. • The increase on mRNA FECH was not reflected in the amount of protein. • FECH could be another control point in heme synthesis. General Significance: Data on the STZ-induced transcription of FECH in diabetic animals could give further support to the hypothesis of the existence of molecular mechanisms that establish a connection between carbohydrate homeostasis and the gene expression of key enzymes in the heme biosynthesis pathway.

Source: Biochemistry and Biophysics Reports

DOI: 10.1016/j.bbrep.2025.101989

Authors: Leda María Oliveri, Ana Maria Buzaleh, Esther Noemí Gerez

Institutions: Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Hospital de Clínicas "José de San Martín", Pontificia Universidad Católica Argentina

Language: English

Topic: Porphyrin Metabolism and Disorders

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,700