Dataset Information

A renal function for 2,3-bisphosphoglycerate mutase (BPGM)

ABSTRACT: The enzyme 2,3 bisphosphoglycerate mutase (BPGM) catalyzes the production of 2,3-bisphosphoglycerate (2,3-BPG). The main role of 2,3-BPG is to shift the equilibrium of hemoglobin toward the deoxy-state, accounting for the notion that 2,3-BPG production would appear to be solely useful in cells which contain hemoglobin. 2,3-BPG level determines the baseline O2-Hb affinity at rest, which shows a broad diversity among human population. The kidney is the site of oxygen sensing and erythropoietin synthesis through the action of the hypoxia-inducible factor (HIF) transcription factors, especially HIF-2. We observed a marked BPGM expression in distal parts of renal tubules that is elevated during kidney injury, thus, indicating cellular functions of BPGM not related to oxygen binding to hemoglobin. We, thus, explored the function of renal BPGM, particularly as related to down-stream metabolic effects.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Fibroblast, Cell Culture

SUBMITTER: Michael Mülleder

LAB HEAD: Prof. Michael Fähling

PROVIDER: PXD033095 | Pride | 2025-05-06

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20211025_QEP_KTT_001_50-0082_Faehling_P00_QC-001_dia.raw.Zip	Raw
	20211025_QEP_KTT_002_50-0082_Faehling_P01_siBPGMcontrol4_dia.raw.Zip	Raw
	20211025_QEP_KTT_003_50-0082_Faehling_P01_mockcontrol6_dia.raw.Zip	Raw
	20211025_QEP_KTT_004_50-0082_Faehling_P01_mockcontrol1_dia.raw.Zip	Raw
	20211025_QEP_KTT_005_50-0082_Faehling_P01_mockhyperosm3_dia.raw.Zip	Raw

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Publications

Beyond hemoglobin: Critical role of 2,3-bisphosphoglycerate mutase in kidney function and injury.

Kulow Vera A VA Roegner Kameliya K Labes Robert R Kasim Mumtaz M Mathia Susanne S Czopek Claudia S CS Berndt Nikolaus N Becker Philipp N PN Ter-Avetisyan Gohar G Luft Friedrich C FC Enghard Philipp P Hinze Christian C Klocke Jan J Eckardt Kai-Uwe KU Schmidt-Ott Kai M KM Persson Pontus B PB Rosenberger Christian C Fähling Michael M

Acta physiologica (Oxford, England) 20241018 1

<h4>Aim</h4>2,3-bisphosphoglycerate mutase (BPGM) is traditionally recognized for its role in modulating oxygen affinity to hemoglobin in erythrocytes. Recent transcriptomic analyses, however, have indicated a significant upregulation of BPGM in acutely injured murine and human kidneys, suggesting a potential renal function for this enzyme. Here we aim to explore the physiological role of BPGM in the kidney.<h4>Methods</h4>A tubular-specific, doxycycline-inducible Bpgm-knockout mouse model was g ...[more]

PMID: 39422260

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Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.