Preconditioning with cobalt chloride or desferrioxamine protects oligodendrocyte cell line (MO3.13) from tumor necrosis factor-α-mediated cell death
✍ Scribed by Song-yi Yao; Mohammed Soutto; Subramaniam Sriram
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 377 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Hypoxia‐inducible factor‐1α (HIF‐1α) is a transcription factor induced under hypoxic conditions. HIF‐1α promotes the expression of genes encoding proteins that increase the cellular supply of oxygen and promote survival in periods of cellular stress and availability of cellular energy. We examined the effect of desferrioxamine (DFO) and cobalt chloride (CoCl~2~), two agents known to increase the stability of HIF‐1α, and its effect on the survivability of an oligodendroglial cell line, MO3.13, when cultured with tumor necrosis factor‐α (TNFα). Our studies showed that, unlike a murine microglial cell line (BV‐2), MO3.13 cells do not induce HIF‐1α in the presence of TNFα. MO3.13 cells do stabilize HIF‐1α in the presence of DFO or CoCl~2~. When MO3.13 cell were preconditioned with either DFO or CoCl~2~, addition of TNFα further increased protein levels of HIF‐1α. The mechanisms that underlie the increase in protein levels of HIF ‐1α seen, following addition of TNFα in preconditioned cells is due to an increase in transcription of the HIF‐1α gene. Increased cellular levels of HIF‐1α is associated with improved survival of MO3.13 cells, when cultured with TNFα after a period of preconditioning by DFO or CoCl~2~. These studies suggest that compoundsthat increase HIF‐1α can function as neuroprotective agents in inflammatory disorders of the CNS. © 2008 Wiley‐Liss, Inc.