Aminopeptidase N mediates the utilization of the GSH precursor CysGly by cultured neurons.

Abstract:

:Neurons in culture rely on the supply of exogenous cysteine for their glutathione synthesis. After application of cysteine to neuron-rich primary cultures, the glutathione content was doubled after a 4-hr incubation. The dipeptide cysteinylglycine (CysGly) was able to substitute for cysteine as exogenous glutathione precursor. In kidneys, the ectopeptidase aminopeptidase N (ApN) has been reported to hydrolyze CysGly. Expression of mRNA of ApN in rat brain and cultured rat neurons was demonstrated by reverse transcriptase polymerase chain reaction and sequencing of the cDNA fragment obtained. In addition, the presence of ApN protein in cultured neurons was demonstrated by its immunocytochemical localization. In the presence of an activity-inhibiting antiserum against ApN the utilization of CysGly as neuronal glutathione precursor was completely prevented, whereas that of cysteine plus glycine was not affected. The data presented demonstrates that cultured rat neurons express ApN and that this ectopeptidase participates in the utilization of CysGly as precursor for neuronal glutathione.

journal_name

J Neurosci Res

authors

Dringen R,Gutterer JM,Gros C,Hirrlinger J

doi

10.1002/jnr.10042

keywords:

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

1003-8

issue

5

eissn

0360-4012

issn

1097-4547

pii

10.1002/jnr.10042

journal_volume

66

pub_type

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