Hypoxia upregulates amino acid transport in a human neuroblastoma cell line

Background/PurposeSome 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.MethodsCells were incubated under hypoxic conditions (1% O2–5% CO2–94% N2). After 0, 8, 16, and 24 hours, the transport of 3H-glutamine, 3H-glutamate, and 3H-leucine was assayed. 3H-Thymidine and 3H-leucine incorporation was measured for the determination of DNA and protein synthesis, respectively.ResultsHypoxia 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 Vmax without affecting Km. 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).ConclusionsThis 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.