Uptake, metabolism and toxicity of hemin in cultured neurons.

Abstract:

:Following hemorrhagic stroke, red blood cells lyse and release neurotoxic hemin into the interstitial space. The present study investigates whether neurons can accumulate and metabolize hemin. We demonstrate that cultured neurons express the heme carrier protein 1 (HCP1), and that this transporter appears to contribute to the time- and concentration-dependent accumulation of hemin by neurons. Although exposure of neurons to hemin stimulates the synthesis of the iron storage protein ferritin, approximately 80% of the hemin accumulated by neurons remains intact. Within 24h of incubation, substantial neurotoxicity was observed that was not attenuated by the cell permeable, selective ferrous iron chelator, 1,10-phenanthroline. These results demonstrate that while neurons efficiently accumulate hemin they slowly degrade it, and they support the conclusion that intact hemin is more neurotoxic than the iron released from the breakdown of hemin. Further investigations are required to determine the basis of this neurotoxicity.

journal_name

Neurochem Int

authors

Dang TN,Robinson SR,Dringen R,Bishop GM

doi

10.1016/j.neuint.2011.03.006

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

804-11

issue

7

eissn

0197-0186

issn

1872-9754

pii

S0197-0186(11)00099-4

journal_volume

58

pub_type

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