Aromatic amino acid activation of signaling pathways in bone marrow mesenchymal stem cells depends on oxygen tension

Mona El Refaey, Qing Zhong, William D Hill, Xing Ming Shi, Mark W Hamrick, Lakiea Bailey, Maribeth H Johnson, Jianrui Xu, Wendy B Bollag, Norman Chutkan, Carlos M Isales

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The physiologic oxygen pressures inside the bone marrow environment are much lower than what is present in the peripheral circulation, ranging from 1-7%, compared to values as high as 10-13% in the arteries, lungs and liver. Thus, experiments done with bone marrow mesenchymal stem cells (BMMSCs) using standard culture conditions may not accurately reflect the true hypoxic bone marrow microenvironment. However, since aging is associated with an increased generation of reactive oxygen species, experiments done under 21%O2 conditions may actually more closely resemble that of the aging bone marrow environment. Aromatic amino acids are known to be natural anti-oxidants. We have previously reported that aromatic amino acids are potent agonists for stimulating increases in intracellular calcium and phospho-c-Raf and in promoting BMMSC differentiation down the osteogenic pathway. Our previous experiments were performed under normoxic conditions. Thus, we next decided to compare a normoxic (21% O2) vs. a hypoxic environment (3% O 2) alone or after treatment with aromatic amino acids. Reverse-phase protein arrays showed that 3% O2 itself up-regulated proliferative pathways. Aromatic amino acids had no additional effect on signaling pathways under these conditions. However, under 21%O2 conditions, aromatic amino acids could now significantly increase these proliferative pathways over this "normoxic" baseline. Pharmacologic studies are consistent with the aromatic amino acids activating the extracellular calcium-sensing receptor. The effects of aromatic amino acids on BMMSC function in the 21% O2 environment is consistent with a potential role for these amino acids in an aging environment as functional anti oxidants.

Original languageEnglish (US)
Article numbere91108
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 11 2014

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Aromatic Amino Acids
bone marrow cells
Stem cells
Mesenchymal Stromal Cells
aromatic compounds
stem cells
Bone
Bone Marrow
Chemical activation
Oxygen
oxygen
amino acids
bone marrow
Aging of materials
Oxidants
oxidants
Calcium-Sensing Receptors
Protein Array Analysis
calcium
Experiments

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Aromatic amino acid activation of signaling pathways in bone marrow mesenchymal stem cells depends on oxygen tension. / Refaey, Mona El; Zhong, Qing; Hill, William D; Shi, Xing Ming; Hamrick, Mark W; Bailey, Lakiea; Johnson, Maribeth H; Xu, Jianrui; Bollag, Wendy B; Chutkan, Norman; Isales, Carlos M.

In: PloS one, Vol. 9, No. 4, e91108, 11.04.2014.

Research output: Contribution to journalArticle

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