Over-expression of heme oxygenase-1 promotes oxidative mitochondrial damage in rat astroglia
Article first published online: 12 OCT 2005
Copyright © 2005 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 206, Issue 3, pages 655–663, March 2006
How to Cite
Song, W., Su, H., Song, S., Paudel, H. K. and Schipper, H. M. (2006), Over-expression of heme oxygenase-1 promotes oxidative mitochondrial damage in rat astroglia. J. Cell. Physiol., 206: 655–663. doi: 10.1002/jcp.20509
- Issue published online: 16 DEC 2005
- Article first published online: 12 OCT 2005
- Manuscript Accepted: 26 JUL 2005
- Manuscript Received: 20 JUL 2005
- Valorisation-Recherche Québec (HMS, HP)
- Canadian Institutes of Health Research (HMS)
Glial heme oxygenase-1 is over-expressed in the CNS of subjects with Alzheimer disease (AD), Parkinson disease (PD) and multiple sclerosis (MS). Up-regulation of HO-1 in rat astroglia has been shown to facilitate iron sequestration by the mitochondrial compartment. To determine whether HO-1 induction promotes mitochondrial oxidative stress, assays for 8-epiPGF2α (ELISA), protein carbonyls (ELISA) and 8-OHdG (HPLC-EC) were used to quantify oxidative damage to lipids, proteins, and nucleic acids, respectively, in mitochondrial fractions and whole-cell compartments derived from cultured rat astroglia engineered to over-express human (h) HO-1 by transient transfection. Cell viability was assessed by trypan blue exclusion and the MTT assay, and cell proliferation was determined by [3H] thymidine incorporation and total cell counts. In rat astrocytes, hHO-1 over-expression (×3 days) resulted in significant oxidative damage to mitochondrial lipids, proteins, and nucleic acids, partial growth arrest, and increased cell death. These effects were attenuated by incubation with 1 µM tin mesoporphyrin, a competitive HO inhibitor, or the iron chelator, deferoxamine. Up-regulation of HO-1 engenders oxidative mitochondrial injury in cultured rat astroglia. Heme-derived ferrous iron and carbon monoxide (CO) may mediate the oxidative modification of mitochondrial lipids, proteins and nucleic acids in these cells. Glial HO-1 hyperactivity may contribute to cellular oxidative stress, pathological iron deposition, and bioenergetic failure characteristic of degenerating and inflamed neural tissues and may constitute a rational target for therapeutic intervention in these conditions. © 2005 Wiley-Liss, Inc.