Effect of heme oxygenase-1 on the vulnerability of astrocytes and neurons to hemoglobin.
The heme oxygenase (HO) enzymes catalyze the rate-limiting step of heme breakdown. Prior studies have demonstrated that the vulnerability of neurons and astrocytes to hemoglobin is modified in cells lacking HO-2, the constitutive isoform. The present study assessed the effect of the inducible isoform, HO-1. Wild-type astrocytes treated for 3-5 days with 3-30 microM hemoglobin sustained no loss of viability, as quantified by LDH and MTT assays. The same treatment resulted in death of 25-50% of HO-1 knockout astrocytes, and a 4-fold increase in protein oxidation. Cell injury was attenuated by transfer of the HO-1 gene, but not by bilirubin, the antioxidant heme breakdown product. Conversely, neuronal protein oxidation and cell death after hemoglobin exposure were similar in wild-type and HO-1 knockout cultures. These results suggest that HO-1 induction protects astrocytes from the oxidative toxicity of Hb, but has no effect on neuronal injury.
Chen-Roetling
Jing
J
Thomas Jefferson University, 1020 Sansom Street, Thompson 239, Philadelphia, PA 19107, USA.
Regan
Raymond F
RF
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology*; D001663:Bilirubin / Q000494:pharmacology; D017353:Gene Deletion; D018014:Gene Transfer Techniques; D051547:Heme Oxygenase-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology*
D006454:Hemoglobins; D006427:Hemin; D051547:Heme Oxygenase-1; D001663:Bilirubin