Journal
MOLECULAR MEDICINE REPORTS
Volume 14, Issue 5, Pages 4706-4714Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2016.5796
Keywords
hypoxia; adipose-derived stem cells; lactate production; glucose uptake; proliferation
Categories
Funding
- National Research Foundation
- Korean government [2014054836]
- Chung-Ang University Research Grants
Ask authors/readers for more resources
It has previously been demonstrated that hypoxia has diverse stimulatory effects on adipose-derived stem cells (ASCs), however, metabolic responses under hypoxia remain to be elucidated. Thus, the present study aimed to investigate the glucose uptake and metabolism of ASCs under hypoxic conditions, and to identify the underlying molecular mechanisms. ASCs were cultured in 1% oxygen, and experiments were conducted in vitro. As determined by proteomic analysis and western blotting, GAPDH and enolase 1 (ENO1) expression were upregulated under hypoxia. In addition, lactate production was significantly increased, and mRNA levels of glycolytic enzymes, including GAPDH, ENO1, hexokinase 2 (HK2), and lactate dehydrogenase a (LDH alpha) were upregulated. Hypoxia-inducible factor 1-alpha (HIF-1 alpha) expression was increased as demonstrated by western blotting, and a pharmacological inhibitor of HIF-1 alpha significantly attenuated hypoxia-induced lactate production and expression of glycolytic enzymes. It was also observed that hypoxia significantly increased glucose uptake in ASCs, and glucose transporter (GLUT) 1 and GLUT3 expression were upregulated under hypoxia. Pharmacological inhibition of the HIF-1 alpha signaling pathways also attenuated hypoxia-induced GLUT1 and GLUT3 expression. These results collectively indicate that hypoxia increases glucose uptake via GLUT1 and GLUT3 upregulation, and induces lactate production of ASCs via GAPDH, ENO1, HK2, and LDH alpha. Furthermore, HIF-1 alpha is involved in glucose uptake and metabolism of ASCs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available