Open AccessGlut1 expression is increased by p53 reduction to switch metabolism to glycolysis during osteoblast differentiation
Author(s) -
Tomokazu Ohnishi,
Joji Kusuyama,
Kenjiro Bandow,
Tetsuya Matsuguchi
Publication year - 2020
Publication title -
biochemical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.706
H-Index - 265
eISSN - 1470-8728
pISSN - 0264-6021
DOI - 10.1042/bcj20190888
Subject(s) - glycolysis , glut1 , hexokinase , osteoblast , pyruvate kinase , chemistry , glucose transporter , oxidative phosphorylation , pi3k/akt/mtor pathway , protein kinase b , phosphorylation , biology , microbiology and biotechnology , biochemistry , signal transduction , metabolism , endocrinology , insulin , in vitro
The glycolytic system is selected for ATP synthesis not only in tumor cells but also in differentiated cells. Differentiated osteoblasts also switch the dominant metabolic pathway to aerobic glycolysis. We found that primary osteoblasts increased expressions of glycolysis-related enzymes such as Glut1, hexokinase 1 and 2, lactate dehydrogenase A and pyruvate kinase M2 during their differentiation. Osteoblast differentiation decreased expression of tumor suppressor p53, which negatively regulates Glut1 expression, and enhanced phosphorylation of AKT, which is regulated by phosphoinositol-3 kinase (PI3K). An inhibitor of PI3K enhanced p53 expression and repressed Glut1 expression. Luciferase reporter assay showed that p53 negatively regulated transcriptional activity of solute carrier family 2 member 1 gene promoter region. Inhibition of glycolysis in osteoblasts reduced ATP contents more significantly than inhibition of oxidative phosphorylation by carbonyl cyanide m-chlorophenyl hydrazine. These results have indicated that osteoblasts increase Glut1 expression through the down-regulation of p53 to switch their metabolic pathway to glycolysis during differentiation.