Effects of Thyroid Hormone and Hypoxia on 2,3-Bisphosphoglycerate, Bisphosphoglycerate Synthase and Phosphoglycerate Mutase in Rabbit Erythroblasts and Reticulocytes in vivo

Abstract

Objectives: The effects of triiodothyronine (T₃) and hypoxia on 2,3-bisphosphoglycerate (2,3-BPG) studied in vitro are unclear. To clarify these effects we selected a more physiologic approach: the in vivo study in rabbits. We also present the changes produced by T₃ and hypoxia on phosphoglycerate mutase (PGAM), which requires 2,3-BPG as a cofactor, and 2,3-BPG synthase (BPGS), the enzyme responsible for 2,3-BPG synthesis in erythroblasts and reticulocytes. Methods: Hyperthyroidism was induced by daily T₃ injection (250 µg/kg), hypoxia by a mixture of 90% nitrogen and 10% oxygen and hypothyroidism by propylthiouracil (PTU) added to drinking water. Results: Both T₃ administration and hypoxic conditions increased 2,3-BPG levels and BPGS mRNA levels and activity in erythroblasts but not in reticulocytes. Unlike BPGS, both PGAM mRNA levels and activity were increased in erythroblasts and reticulocytes under hyperthyrodism and hypoxia. The antihormone PTU produced opposite effects to T₃. Conclusion: The results presented here suggest that both hyperthyroidism and hypoxia modulate in vivo red cell 2,3-BPG content by changes in the expression of BPGS. Similarly, the changes in PGAM activity are also explained by changes in its expression.

Expression Profiling Reveals Novel Hypoxic Biomarkers in Peripheral Blood of Adult Mice Exposed to Chronic Hypoxia

“…The significant increase partially overlapped with the increased relative amount of reticulocytes on CH-7. This difference may be explained by the proliferation of reticulocytes induced by hypoxia [59]. Nevertheless, the expression of CD36 was completely suppressed by REC, suggesting that reticulocyte proliferation activity was also reduced during REC.…”

A Translational In Vivo and In Vitro Metabolomic Study Reveals Altered Metabolic Pathways in Red Blood Cells of Type 2 Diabetes

“…The metabolomic changes could be potential indicators of DM2 comorbidities. For instance, increased 2,3-BPG levels have been associated with hyperthyroidism and problems of O 2 transport and delivery by RBCs in DM2 [ 74 , 75 , 78 ] while IMP could be related with the risk of haemolysis and membrane hyperpolarisation of RBCs, as well as haemoglobin deoxygenation [ 79 , 80 , 81 , 82 ]. GSH levels could also be related to ROS present in cardiovascular complications.…”

Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma

“…Most intriguingly, we found that phosphoglycerate mutase 1 (PGAM1) was shown an upregulation up to 6-fold. As an enzyme in glycolysis, PGAM1 was ubiquitously expressed in human , Bacillus stearothermophilus [38], Escherichia coli [39], Entamoeba histolytica [40], et al , functions to catalyze the interconversion of 3-phosphoglycerate and 2-phosphoglycerate with 2,3-bisphosphoglycerate (2,3-BPG) [15,41]. A recent study revealed that PGAM1 was overexpressed in breast cancer, and suppression PGAM1 expression displayed a profound antiproliferative effect, underscoring its important role in carcinogenesis [14].…”