| α-Lipoic Acid Inhibits TNF-α-Induced Apoptosis in Human Bone
Marrow Stromal Cells by Reduction of Oxidative Stress
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| 알파 리포산에 의한 산화 스트레스의 감소로 TNF-α에 의한
사람 골수기질세포의 세포자멸사 억제
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| 고정민1,변창현2,이희숙2,이영선2,김기수1 |
| 울산대학교 의과대학 서울아산병원 내과학교실1, 아산생명과학 연구소2 |
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| Abstract |
Background
Oxidative stress is an important mediator of bone loss. In cells with specific TNF receptors, TNF-α, a mediator of bone loss following menopause, increases intracellular oxidative stress.
Methods
In the HS-5 human bone marrow stromal cell line (hBMSC), we tested effects of TNF-α or H2O2 on cell viability and apoptosis, using MTT-dye reduction microassay, trypan blue exclusion, Cell Death Detection ELISA assay and caspase-3 activity. Intracellular state of oxidative stress was determined by the generation of excessive reactive oxygen species (ROS) and total glutathione content. We also tested whether α-lipoic acid (α-LA), an important biological thiol antioxidant, can protect hBMSC against TNF-α-induced apoptosis.
Results
Both TNF-α and H2O2 reduced cell viability of hBMSC, increased apoptosis of hBMSC with reversal by pan-caspase inhibitor, and activated caspase-3. Both increased intracellular ROS up to 162.3±7.5% and 177.5±4.1%, respectively, and reduced total glutathione content up to 49.8±1.7% and 43.4±2.9%, respectively. These changes by TNF-α and H2O2 were completely reversed by α-LA.
Conclusions
Our data show that TNF-α-induced hBMSC apoptosis is mediated by increased intracellular ROS with blocking by α-LA. These suggest that α-LA may have therapeutic applications in halting or attenuating bone loss associated with increased oxidative stress.
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| Key Words:
Thioctic acid, Tumor necrosis factor, Human bone marrow stromal cells, Apoptosis, Antioxidants |
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