Hemehemopexin complex attenuates neuronal cell death and stroke damage

Rung Chi Li, Sofiyan Saleem, Gehua Zhen, Wangsen Cao, Hean Zhuang, Jongseok Lee, Ann Smith, Fiorella Altruda, Emanuela Tolosano, Sylvain Doré

Research output: Contribution to journalArticlepeer-review

Abstract

Hemoproteins undergo degradation during hypoxic ischemic conditions, but the pro-oxidant free heme that is released cannot be recycled and must be degraded. The extracellular heme associates with its high-affinity binding protein, hemopexin (HPX). Hemopexin is shown here to be expressed by cortical neurons and it is present in mouse cerebellum, cortex, hippocampus, and striatum. Using the transient ischemia model (90-min middle cerebral artery occlusion followed by 96-h survival), we provide evidence that HPX is protective in the brain, as neurologic deficits and infarct volumes were significantly greater in HPX than in wild-type mice. Addressing the potential protective HPX cellular pathway, we observed that exogenous free heme decreased cell survival in primary mouse cortical neuron cultures, whereas the heme bound to HPX was not toxic. Heme HPX complexes induce HO1 and, consequently, protect primary neurons against the toxicity of both heme and pro-oxidant tert-butyl hydroperoxide; such protection was decreased in HO1 neuronal cultures. Taken together, these data show that HPX protects against heme-induced toxicity and oxidative stress and that HO1 is required. We propose that the heme HPX system protects against stroke-related damage by maintaining a tight balance between free and bound heme. Thus, regulating extracellular free heme levels, such as with HPX, could be neuroprotective.

Original languageEnglish (US)
Pages (from-to)953-964
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume29
Issue number5
DOIs
StatePublished - May 2009

Keywords

  • Heme oxygenase
  • Hemopexin
  • Middle cerebral artery occlusion
  • Transient ischemic stroke

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Hemehemopexin complex attenuates neuronal cell death and stroke damage'. Together they form a unique fingerprint.

Cite this