Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Effects of GABA on Erythropoiesis in the Hep3B Cell and Rat Exposed to Hypoxia

  • Yoon, Joongsoo (Department of Clinical Laboratory Science, Kyungdong University) ;
  • Sim, In-Suk (Department of Clinical Laboratory Science, Kyungdong University)
  • Received : 2021.04.15
  • Accepted : 2021.06.04
  • Published : 2021.06.30
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Abstract

The aim of this study was to evaluate gamma-aminobutyric acid (GABA)-induced erythropoietin (EPO) and EPO-receptor expression in human Hep3B cells and Sprague Dawley (SD) rats during hypoxia. Expression levels of EPO, EPO-R mRNA, Janus kinase-2 (JAK-2), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1), and HIF-2 in response to GABA treatment were evaluated in cell lines. SD rats were randomly divided into 5 groups of 8 rats each, and GABA was orally administered; the groups were the normal control (NC), hypoxia-exposed (G0), as well as the GABA 1 mg/100 g body weight (BW) GABA treated group (G1), 5 mg/100 g BW GABA treated group (G5), and 10 mg/100 g BW GABA treated group (G10) with hypoxia. We analyzed EPO levels and red blood cell counts in rat blood and EPO gene expression in kidney tissue. EPO and VEGF mRNA levels in Hep3B cells exposed to hypoxia were significantly increased and further increased after GABA treatment. However, the expression of EPO-R and JAK-2 mRNAs were not affected by GABA, but hypoxia-induced HIF-1 and HIF-2 mRNA expression was inhibited by GABA. In the kidney tissue of rats exposed to hypoxia, the expression level of EPO mRNA was greatly increased, but levels in the GABA treatment groups significantly decreased. EPO levels in the serum showed the same significant trend, but the red blood cell counts were not significantly different. These findings demonstrate that HIF-1 and HIF-2 activation increase EPO expression in Hep3B cells exposed to hypoxia. However HIF decreased by GABA addition and VEGF increased significantly.

Keywords

Acknowledgement

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (No. 2018R1C1B5086313).

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