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Research Database PMU-SQQUID

Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply.
Spoden, GA; Rostek, U; Lechner, S; Mitterberger, M; Mazurek, S; Zwerschke, W;
Exp Cell Res. 2009; 315(16):2765-2774
Originalarbeiten (Zeitschrift)

PMU-Authors

Mitterberger Michael

Abstract

The glycolytic key regulator pyruvate kinase M2 (M2-PK or PKM2) call switch between a highly active tetrameric and all inactive dimeric form. The transition between the two conformations regulates the glycolytic flux in tumor cells. We developed specific M2-PK-binding peptide aptamers which inhibit M2-PK, but not the 96% homologous M1-PK isoenzyme. In this Study we demonstrate that, at normal blood glucose concentrations, peptide aptamer-mediated inhibition of M2-PK induces a significant decrease of the population doubling (PDL rate) and cell proliferation rate as well as all increase in cell size, whereas Under glucose restriction in increase in PDL and cell proliferation rates but a decrease in cell size was observed. Moreover, M2-PK inhibition rescues cells from glucose starvation-induced apoptotic cell death by increasing the metabolic activity. These findings Suggest that M2-PK is a metabolic sensor which regulates Cell proliferation, cell growth and apoptotic cell death in a glucose supply-dependent manner. (C) 2009 Elsevier Inc. All rights reserved.


Useful keywords (using NLM MeSH Indexing)

Amino Acid Sequence

Animals

Apoptosis/physiology*

Aptamers, Peptide/genetics

Aptamers, Peptide/metabolism

Cell Proliferation*

Cell Size

Energy Metabolism*

Glucose/metabolism*

Glycolysis*

Humans

Isoenzymes/genetics

Isoenzymes/metabolism*

Mice

Molecular Sequence Data

NIH 3T3 Cells

Pyruvate Kinase/genetics

Pyruvate Kinase/metabolism*


Find related publications in this database (Keywords)

Apoptosis
Caloric restriction
PKM2
Proliferation
Growth
Metabolic activity