Skip to Content
MilliporeSigma
  • Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells.

Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells.

Nature communications (2021-01-17)
Ratnasekhar Ch, Guillaume Rey, Sandipan Ray, Pawan K Jha, Paul C Driscoll, Mariana Silva Dos Santos, Dania M Malik, Radoslaw Lach, Aalim M Weljie, James I MacRae, Utham K Valekunja, Akhilesh B Reddy
ABSTRACT

Circadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
3-(Trimethylsilyl)-1-propanesulfonic acid-d6 sodium salt, 98 atom % D
Sigma-Aldrich
6-Aminonicotinamide, 99%
Sigma-Aldrich
Anti-Rabbit IgG (whole molecule)–Peroxidase antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Bovine Serum Albumin, heat shock fraction, pH 7, ≥98%
Sigma-Aldrich
Krebs-Henseleit Buffer Modified, With 2000 mg/L glucose, without calcium chloride and sodium bicarbonate, powder, suitable for cell culture
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium, Without glucose, L-glutamine, phenol red, sodium pyruvate and sodium bicarbonate, powder, suitable for cell culture
Sigma-Aldrich
Sodium bicarbonate solution, solution (7.5%), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose, sodium pyruvate, and sodium bicarbonate, without L-glutamine, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Picropodophyllotoxin, ≥96% (HPLC), powder
Sigma-Aldrich
Deuterium oxide, 99.9 atom % D
Sigma-Aldrich
MEM Non-essential Amino Acid Solution (100×), without L-glutamine, liquid, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
HEPES solution, 1 M, pH 7.0-7.6, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
L-(−)-Glucose, ≥99%
Sigma-Aldrich
D-(+)-Glucose solution, 100 g/L in H2O, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
Newborn Bovine Serum, New Zealand origin