Nitric oxide signaling is disrupted in the yeast model for Batten disease.

Abstract:

:The juvenile form of neuronal ceroid lipofuscinoses (JNCLs), or Batten disease, results from mutations in the CLN3 gene, and it is characterized by the accumulation of lipopigments in the lysosomes of several cell types and by extensive neuronal death. We report that the yeast model for JNCL (btn1-Delta) that lacks BTN1, the homologue to human CLN3, has increased resistance to menadione-generated oxidative stress. Expression of human CLN3 complemented the btn1-Delta phenotype, and equivalent Btn1p/Cln3 mutations correlated with JNCL severity. We show that the previously reported decreased levels of L-arginine in btn1-Delta limit the synthesis of nitric oxide (.NO) in both physiological and oxidative stress conditions. This defect in .NO synthesis seems to suppress the signaling required for yeast menadione-induced apoptosis, thus explaining btn1-Delta phenotype of increased resistance. We propose that in JNCL, a limited capacity to synthesize .NO directly caused by the absence of Cln3 function may contribute to the pathology of the disease.

journal_name

Mol Biol Cell

authors

Osório NS,Carvalho A,Almeida AJ,Padilla-Lopez S,Leão C,Laranjinha J,Ludovico P,Pearce DA,Rodrigues F

doi

10.1091/mbc.e06-11-1053

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

2755-67

issue

7

eissn

1059-1524

issn

1939-4586

pii

E06-11-1053

journal_volume

18

pub_type

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