Hypoxia upregulates amino acid transport in a human neuroblastoma cell line

Background/Purpose: Some tumor cells survive and even grow in hypoxic conditions. We examined the effect of hypoxia on amino acid transport in a human neuroblastoma cell line SK-N-SH. Methods: Cells were incubated under hypoxic conditions (1% O-2-5% CO2-94% N-2). After 0, 8, 16, and 24 hours, the transport of H-3-glutamine, H-3-glutamate, and H-3-leucine was assayed. H-3-Thymidine and H-3-leucine incorporation was measured for the determination of DNA and protein synthesis, respectively. Results: Hypoxia increased Na+-dependent glutamine and Na+-independent leucine transport significantly at 16 and 24 hours compared with control (P < .01) by a mechanism that increased V-max without affecting K-m. These increases were completely blocked by actinomycin D and cycloheximide. There was no significant difference in Na+-dependent glutamate transport between control and hypoxic groups. DNA and protein synthesis significantly decreased in the hypoxic condition compared with control (P <.01). Conclusions: This study demonstrated that hypoxia upregulates amino acid transport in a human neuroblastoma cell line. This mechanism may allow cells to survive and even grow under hypoxic conditions. (C) 2007 Elsevier Inc. All rights reserved.