Oncotarget

Research Papers:

Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation

Henry Oppermann, Lutz Schnabel, Jürgen Meixensberger and Frank Gaunitz _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:85848-85860. https://doi.org/10.18632/oncotarget.13039

Metrics: PDF 2952 views  |   HTML 2397 views  |   ?  


Abstract

Henry Oppermann1,*, Lutz Schnabel1,*, Jürgen Meixensberger1, Frank Gaunitz1

1Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig AöR, 04103 Leipzig, Germany

*These authors contributed equally to this work

Correspondence to:

Frank Gaunitz, email: [email protected]

Keywords: glioblastoma, carnosine, glycolysis, glucose, pyruvate

Received: August 23, 2016     Accepted: October 27, 2016     Published: November 03, 2016

ABSTRACT

Here we analyzed whether the anti-neoplastic effect of carnosine, which inhibits glycolytic ATP production, can be antagonized by ATP production via oxidative phosphorylation fueled by pyruvate. Therefore, glioblastoma cells were cultivated in medium supplemented with glucose, galactose or pyruvate and in the presence or absence of carnosine. CPI-613 was employed to inhibit the entry of pyruvate into the tricarboxylic acid cycle and 2,4-dinitrophenol to inhibit oxidative phosphorylation. Energy metabolism and viability were assessed by cell based assays and histochemistry.

ATP in cell lysates and dehydrogenase activity in living cells revealed a strong reduction of viability under the influence of carnosine when cells received glucose or galactose but not in the presence of pyruvate. CPI-613 and 2,4-dinitrophenol reduced viability of cells cultivated in pyruvate, but no effect was seen in the presence of glucose. No effect of carnosine on viability was observed in the presence of glucose and pyruvate even in the presence of 2,4-dinitrophenol or CPI-613.

In conclusion, glioblastoma cells produce ATP from pyruvate via the tricarboxylic acid cycle and oxidative phosphorylation in the absence of a glycolytic substrate. In addition, pyruvate attenuates the anti-neoplastic effect of carnosine, even when ATP production via tricarboxylic acid cycle and oxidative phosphorylation is blocked. We also observed an inhibitory effect of carnosine on the tricarboxylic acid cycle and a stimulating effect of 2,4-dinitrophenol on glycolytic ATP production.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 13039