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Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells (GC-MS)

ABSTRACT:

Circadian clocks coordinate mammalian behaviour 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.

GC-MS assay protocols and data are reported in the current study MTBLS1286.

LC-MS assay protocols and data for this study are reported in MTBLS1285.

INSTRUMENT(S): Gas Chromatography MS - positive

SUBMITTER: Ratnasekhar Ch

PROVIDER: MTBLS1286 | MetaboLights | 2020-11-13

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS1286	Other
	FILES	Other
	a_MTBLS1286_GC-MS_positive__metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS1286_GC-MS_positive__metabolite_profiling_v2_maf.tsv	Tabular

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Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells (LC-MS)

Project description:Circadian clocks coordinate mammalian behaviour 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. LC-MS assay protocols and data are reported in the current study MTBLS1285.GC-MS assay protocols and data for this study are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1286' rel='noopener noreferrer' target='_blank'>MTBLS1286</a>.

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