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Essential role of lactate in controlling the rapid proliferation of pulmonary microvascular endothelial cells
Author(s) -
ParraBonilla Glenda,
Alvarez Diego F,
AlMehdi AbuBakr,
Stevens Troy
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1024.12
Subject(s) - glycolysis , lactate dehydrogenase , lactic acid , cell growth , biochemistry , warburg effect , galactose , enzyme , chemistry , biology , microbiology and biotechnology , bacteria , genetics
Pulmonary microvascular endothelial cells (PMVECs) constitutively up‐regulate glycolytic enzymes necessary to generate ATP. One of these enzymes is lactate dehydrogenase (LDH), which converts pyruvate to lactate, causing lactic acidosis in proliferating cells. Since the role of LDH and lactate in endothelial pro‐proliferation is unknown, we tested whether lactate is a key contributor of rapid PMVEC proliferation. PMVEC growth curves were generated using standard culture conditions (10% serum with 22 mM glucose) in the presence of the LDH inhibitor, oxamate (4, 8 and 16 mM). Oxamate inhibited growth, glucose consumption and lactate production in a dose‐dependent manner, suggesting that conversion of pyruvate to lactate is essential for rapid proliferation. To determine whether glycolytic flux is necessary to sustain proliferation, galactose was substituted for glucose, since galactose is an ineffective glycolysis substrate. Galactose treatment reduced cellular ATP concentrations ?2‐fold, and inhibited growth, glucose consumption and lactate production. To examine whether lactate results in glycolytic‐independent cell growth, lactate was added to galactose‐rich media. Addition of exogenous lactate restored cellular ATP concentrations and partially rescued PMVEC proliferation. Thus, LDH contributes to the rapid PMVEC proliferation by controlling the rate of pyruvate conversion to lactate.