Regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type I
Background: 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 expressi...
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Elsevier
2025-06-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825000767 |
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| author | Leda María Oliveri Ana Maria Buzaleh Esther Noemí Gerez |
| author_facet | Leda María Oliveri Ana Maria Buzaleh Esther Noemí Gerez |
| author_sort | Leda María Oliveri |
| collection | DOAJ |
| description | Background: 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. Methods: 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). Results: 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. Conclusions: 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. |
| format | Article |
| id | doaj-art-22e59aa9f4cf44f0a6442e67b51ea143 |
| institution | DOAJ |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-22e59aa9f4cf44f0a6442e67b51ea1432025-08-20T03:22:35ZengElsevierBiochemistry and Biophysics Reports2405-58082025-06-014210198910.1016/j.bbrep.2025.101989Regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type ILeda María Oliveri0Ana Maria Buzaleh1Esther Noemí Gerez2Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, ArgentinaCentro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, ArgentinaCentro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), UBA-CONICET, Hospital de Clínicas José de San Martín, Argentina; Cátedra Bioquímica General Celular y Molecular, Facultad de Ciencias Médicas. Universidad Católica Argentina (UCA), Buenos Aires, Argentina; Corresponding author. Av. Córdoba 2351, 1120, BUENOS AIRES, Argentina.Background: 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. Methods: 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). Results: 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. Conclusions: 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.http://www.sciencedirect.com/science/article/pii/S2405580825000767DiabetesFerrochelataseVanadateSp1O-GlcNAcylation |
| spellingShingle | Leda María Oliveri Ana Maria Buzaleh Esther Noemí Gerez Regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type I Biochemistry and Biophysics Reports Diabetes Ferrochelatase Vanadate Sp1 O-GlcNAcylation |
| title | Regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type I |
| title_full | Regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type I |
| title_fullStr | Regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type I |
| title_full_unstemmed | Regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type I |
| title_short | Regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type I |
| title_sort | regulation of the expression of ferrochelatase in a murine model of diabetes mellitus type i |
| topic | Diabetes Ferrochelatase Vanadate Sp1 O-GlcNAcylation |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825000767 |
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