Aromatic amino acid activation of signaling pathways in bone marrow mesenchymal stem cells depends on oxygen tension.
Aromatic amino acid activation of signaling pathways in bone marrow mesenchymal stem cells depends on oxygen tension.
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DOI：
10.1371/journal.pone.0091108
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Isales CM
中科院分区：
文献类型：
--
作者：
El Refaey M;Zhong Q;Hill WD;Shi XM;Hamrick MW;Bailey L;Johnson M;Xu J;Bollag WB;Chutkan N;Isales CM
骨髓环境内的生理氧压远低于外周循环中存在的氧压，范围为1- 7%，而动脉、肺和肝脏中的值高达10-13%。因此，使用标准培养条件对骨髓间充质干细胞（BMMSC）进行的实验可能无法准确反映真实的低氧骨髓微环境。然而，由于衰老与活性氧的产生增加有关，在21%O2条件下进行的实验实际上可能更接近于衰老骨髓环境。已知芳香族氨基酸是天然抗氧化剂。我们以前曾报道，芳香族氨基酸是有效的激动剂，刺激细胞内钙和磷酸-c-Raf的增加，并促进BMMSC分化成骨途径。我们以前的实验是在常氧条件下进行的。因此，我们接下来决定比较常氧环境（21%O2）与缺氧环境（3%O2）单独或用芳香族氨基酸处理后。反相蛋白阵列显示，3%O2本身上调增殖途径。芳香族氨基酸在这些条件下对信号通路没有额外的影响。然而，在21%O2条件下，芳香族氨基酸现在可以显着增加这些增殖途径超过这个“常氧”基线。药理学研究与芳香族氨基酸激活细胞外钙敏感受体一致。芳香族氨基酸在21%O2环境中对BMMSC功能的影响与这些氨基酸在老化环境中作为功能性抗氧化剂的潜在作用一致。
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% O2) 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.
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影响因子：
11.4
作者：
Park, Hyun Jung;Carr, Janai R.;Raychaudhuri, Pradip
通讯作者：
Raychaudhuri, Pradip
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA
影响因子：
3.7
作者：
Arounleut P;Bowser M;Upadhyay S;Shi XM;Fulzele S;Johnson MH;Stranahan AM;Hill WD;Isales CM;Hamrick MW
通讯作者：
Hamrick MW
DOI：
10.1073/pnas.97.9.4814
发表时间：
2000-04-25
影响因子：
11.1
作者：
Conigrave, AD;Quinn, SJ;Brown, EM
通讯作者：
Brown, EM
影响因子：
4.1
作者：
Herberg, Samuel;Fulzele, Sadanand;Hill, William D.
通讯作者：
Hill, William D.