MEDICAL HYPOTHESES AND RESEARCH
VOL. 4, No. 1, January 2008



H. Kondoh, et al. [2008] Med. Hypotheses Res. 4: 29‒36.



A Common Metabolic Profile Shared Between Murine
ES Cells and Primary Cells Bypassing Senescence


Hiroshi Kondoh*, Matilde E. Lleonart, Yasuhiro Nakashima,
Takeshi Maruyama, Masayuki Yokode, Makoto Tanaka,
David Bernard and Jesús Gil

Department of Geriatric Medicine, Department of Cardiovascular Medicine, Graduate
School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-
8507, Japan; Department of Pathology, Hospital Vall de’Hebron, Paseo Vall d’Hebron 119-
129, 08035, Barcelona, Spain; Department of Clinical Innovative Medicine, Translational
Research Center, Department of Social Service, Kyoto University Hospital, Kyoto, Japan;
CNRS UMR 8161, Institut de Biologie de Lille,1 rue du Pr Calmette BP 447, 59021 Lille
Cedex, France; Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College
Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, United
Kingdom


Abstract. Enhanced glycolysis even under 20% oxygen culture condition is the
characteristic property of most cancer cells and it is known as the Warburg effect. The
Warburg effect is well exploited in the clinic, what suggest its undisputed significance in
cancer. However, there have been limited mechanistic insights into its relationship with the
well-characterized molecular and genetic events associated with cellular immortalization. We
recently identified that overexpression of the glycolytic enzyme phosphoglycerate mutase
(PGM) immortalized primary mouse embryonic fibroblasts (MEFs). Immortalized MEFs and
mouse embryonic stem cells (ES cells) display higher glycolytic flux with reduced oxygen
consumption, and present more resistance to oxidative damage than senescent cells. We
discovered an unexpected aspect of the Warburg effect, protecting cells from senescence
effect of oxidative damage. These metabolic properties might contribute to the proliferative
potential of ES cells, which are immortal primary cells without any genetic alteration.


* Correspondence: Dr. Hiroshi Kondoh, Department of Geriatric Medicine, Graduate
School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-
8507, Japan. Tel: 0081 75-751-3777. Fax: 0081 75-771-9784.
E-Mail: hkondoh@kuhp.
kyoto-u.ac.jp



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