Up-regulation of the pentose phosphate pathway and HIF-1α expression during neural progenitor cell induction following glutamate treatment in rat ex vivo retina

Kazuhiro Tokuda, Byron Baron, Chiemi Yamashiro, Yasuhiro Kuramitsu, Takao Kitagawa, Masaaki Kobayashi, Koh Hei Sonoda, Kazuhiro Kimura

Research output: Contribution to journalArticle

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Abstract

The metabolic state influences the regulation of neural stem/progenitor cells. The pentose phosphate pathway (PPP), an alternative metabolic pathway that operates parallel to glycolysis, not only provides key intermediates for biosynthetic reactions but also controls the fate of neural stem/progenitor cells. We have previously shown that glutamate application leads to the induction of neural progenitor cells in mature ex vivo rat retina. In this study, we investigated whether regulation of the PPP might be changed following glutamate treatment of the retina. Immunoblot analysis revealed that the amount of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP as well as that of 6-phosphogluconate dehydrogenase (6PGD), another enzyme in this pathway, increased in the glutamate-treated retina. Consistent with the fact that both these enzymes generate reduced nicotinamide adenine dinucleotide phosphate (NADPH), the amount of NAPDH in the treated retina was significantly higher compared with that in the untreated retina. We also found that both DNA synthesis as well as the expression of fatty acid synthase (FASN) increased significantly in the glutamate-treated retina. Furthermore, hypoxia-inducible factor 1-α (HIF-1α), a positive transcriptional regulator of PPP enzymes, was up-regulated at both messenger RNA (mRNA) and protein levels. Finally, we found the interaction of HIF-1α with the M2 isozyme of pyruvate kinase (PKM2), with this interaction having been shown to contribute to a positive feedback loop in the control of glycolysis. Our results thus show that specific metabolic change in the PPP occurs in the process of neural progenitor cell induction in the mature rat retina.

Original languageEnglish
Pages (from-to)137-144
Number of pages8
JournalCell Biology International
Volume44
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

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Hypoxia-Inducible Factor 1
Pentose Phosphate Pathway
Retina
Glutamic Acid
Up-Regulation
Stem Cells
Neural Stem Cells
Glycolysis
Enzymes
Phosphogluconate Dehydrogenase
Fatty Acid Synthases
Pyruvate Kinase
Glucosephosphate Dehydrogenase
Metabolic Networks and Pathways
NADP
Isoenzymes
Messenger RNA
DNA

All Science Journal Classification (ASJC) codes

  • Cell Biology

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Up-regulation of the pentose phosphate pathway and HIF-1α expression during neural progenitor cell induction following glutamate treatment in rat ex vivo retina. / Tokuda, Kazuhiro; Baron, Byron; Yamashiro, Chiemi; Kuramitsu, Yasuhiro; Kitagawa, Takao; Kobayashi, Masaaki; Sonoda, Koh Hei; Kimura, Kazuhiro.

In: Cell Biology International, Vol. 44, No. 1, 01.01.2020, p. 137-144.

Research output: Contribution to journalArticle

Tokuda, Kazuhiro ; Baron, Byron ; Yamashiro, Chiemi ; Kuramitsu, Yasuhiro ; Kitagawa, Takao ; Kobayashi, Masaaki ; Sonoda, Koh Hei ; Kimura, Kazuhiro. / Up-regulation of the pentose phosphate pathway and HIF-1α expression during neural progenitor cell induction following glutamate treatment in rat ex vivo retina. In: Cell Biology International. 2020 ; Vol. 44, No. 1. pp. 137-144.
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