| Autor: |
Bode, B.P., Reuter, N., Conroy, J.L., Souba, W.W. |
| Zdroj: |
Surgery; August 1998, Vol. 124 Issue: 2 p260-268, 9p |
| Abstrakt: |
Background: Human hepatoma cells extract glutamine at rates severalfold greater than normal hepatocytes through a high-affinity transporter encoded by the ATB^0 gene, which contains two putative phosphorylation sites for protein kinase C (PKC). The studies presented here were undertaken to determine whether System B^0-mediated glutamine uptake regulates hepatoma growth and whether PKC regulates the activity of this transporter. Methods: SK-Hep cells were treated with the PKC activator phorbol 12-myristate 13-acetate (PMA) and the initial-rate transport of glutamine and other nutrients measured at specific times thereafter. Growth rates were monitored during culture +/- PMA or an excess of system B^0 substrates relative to glutamine. Results: PMA treatment exerted a rapid (half-life ~ 15 minutes) concentration-dependent inhibition of glutamine uptake rates to 50% of control values via a posttranslational mechanism that decreased transporter maximum velocity. This effect persisted after 24 hours and was abrogated by the PKC inhibitor staurosporine. PMA also significantly decreased amino acid transport System y^+ and System L activities but not System A. Chronic treatment with PMA (PKC depletion) inhibited SK-Hep growth, as did attenuation of System B^0-mediated glutamine uptake with other B^0 substrates. Conclusions: System B^0-mediated glutamine uptake regulates hepatoma cell growth, whereas PKC influences both processes. (Surgery 1998;124:260-8) |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full Text from ScienceDirect