Advertisement

Assessing a Shift of Glucose Biotransformation by LC-MS/MS-based Metabolome Analysis in Carbon Monoxide-Exposed Cells

  • Naoharu Takano
  • Takehiro Yamamoto
  • Takeshi Adachi
  • Makoto Suematsu
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 662)

Abstract

Carbon monoxide (CO) is the stress-inducible gas generated by heme oxygenase (HO). Although the HO/CO system appears to contribute to cell protection and tissue repair under stress conditions, its mode of actions remains largely unknown. We hypothesized that CO might alter the cellular energetic conditions and thereby modulate oxygen metabolism. To examine this hypothesis, we attempted to establish a method to follow the global flux of 13C-glucose in the cells using metabolomic approaches with liquid chromatography-mass spectrometry (LC-MS/MS). The human monoblastic leukemia cell line U937 was exposed to the CO-releasing molecule (CORM). The CO exposure attenuated the conversion of the mass-labeled glucose to its downstream metabolites, while significantly stimulating its conversion to those for pentose phosphate pathway, suggesting roles of stress-inducible CO in a shift of glucose biotransformation.

Keywords

U937 Cell Pentose Phosphate Pathway Heme Oxygenase Varied Stress Condition Global Flux 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This study is supported in part by Grant-in-Aid for Creative Scientific Research from MEXT, Grant-in-Aid for Young Scientists (B) from MEXT, Health and Labor Science Research Grant on Advanced Medical Technology from MHLW, and Scientific Frontier Research Grant from MEXT.

References

  1. 1.
    Airley RE, and Mobasheri A. Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy. 53(4), 233–256 (2007).PubMedCrossRefGoogle Scholar
  2. 2.
    Suematsu M, and Ishimura Y. The heme oxygenase-carbon monoxide system: a regulator of hepatobiliary function. Hepatology. 31(1), 3–6 (2000).PubMedCrossRefGoogle Scholar
  3. 3.
    Kyokane T, Norimizu S, Taniai H, Yamaguchi T, Takeoka S, Tsuchida E, Naito M, Nimura Y, Ishimura Y, and Suematsu M. Carbon monoxide from heme catabolism protects against hepatobiliary dysfunction in endotoxin-treated rat liver. Gastroenterology.120(5), 1227–1240 (2001).PubMedCrossRefGoogle Scholar
  4. 4.
    Luo B, Groenke K, Takors R, Wandrey C, and Oldiges M. Simultaneous determination of multiple intracellular metabolites in glycolysis, pentose phosphate pathway and tricarboxylic acid cycle by liquid chromatography-mass spectrometry. J. Chromato. A. 1147, 153–164 (2007).CrossRefGoogle Scholar
  5. 5.
    Tian J, Bryk R, Itoh M, Suematsu M, and Nathan C. Variant tricarboxylic acid cycle in My-cobacterium tuberculosis: identification of alpha-ketoglutarate decarboxylase. Proc Natl Acad Sci USA. 102(30), 10670–10675 (2005).PubMedCrossRefGoogle Scholar
  6. 6.
    Ho HY, Cheng ML, and Chiu DT. Glucose-6-phosphate dehydrogenase – from oxidative stress to cellular functions and degenerative diseases. Redox Rep. 12(3), 109–118 (2007).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Naoharu Takano
    • 1
  • Takehiro Yamamoto
    • 1
  • Takeshi Adachi
    • 2
  • Makoto Suematsu
    • 2
  1. 1.Department of Biochemistry & Integrative Medical BiologySchool of Medicine, Keio UniversityTokyoJapan
  2. 2.Department of Biochemistry & Integrative Medical BiologySchool of Medicine, Keio UniversityTokyoJapan

Personalised recommendations