Induction of iNOS expression in ammonia-exposed cultured astrocytes is coupled to increased arginine transport by upregulated y+ LAT2 transporter
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Journal of Neurochemistry
ISSN
0022-3042
EISSN
1471-4159
Wydawca
WILEY-BLACKWELL
URL
Rok publikacji
2015
Numer zeszytu
6
Strony od-do
1272-1281
Numer tomu
135
Link do pełnego tekstu
Identyfikator DOI
Liczba arkuszy
1,32
Słowa kluczowe
en
ammonia
astrocytes
y+LAT2 transporter
arginine
nitric oxide synthase
nitration
Streszczenia
Język
en
Treść
One of the aspects of ammonia toxicity to brain cells is increased production of nitric oxide (NO) by NO synthases (NOSs). Previously we showed that ammonia increases arginine (Arg) uptake in cultured rat cortical astrocytes specifically via y+ L amino acid transport system, by activation of its member, a heteromeric y+ LAT2 transporter. Here, we tested the hypothesis that up-regulation of y+ LAT2 underlies ammonia-dependent increase of NO production via iNOS induction, and protein nitration. Treatment of rat cortical astrocytes for 48 with 5 mM ammonium chloride ("ammonia") i) increased the y+ L-mediated Arg uptake, ii) raised the expression of iNOS and eNOS, iii) stimulated NO production, as manifested by increased nitrite+nitrate (Griess) and/or nitrite alone (chemiluminescence), and consequently, iv) evoked nitration of tyrosine residues of proteins in astrocytes. Except for the increase of eNOS, all the above described effects of ammonia were abrogated by pretreatment of astrocytes with either siRNA silencing of the Slc7a6 gene coding for y+ LAT2 protein, or antibody to y+ LAT2, indicating their strict coupling to y+ LAT2 activity. Moreover, induction of y+ LAT2 expression by ammonia was sensitive to NfκB inhibitor, BAY 11-7085, linking y+ LAT2 upregulation to the NfκB activation in this experimental setting as reported earlier and here confirmed. Importantly, ammonia did not affect y+ LAT2 expression nor y+ L -mediated Arg uptake activity in the cultured cerebellar neurons, suggesting astroglia-specificity of the above described mechanism. The described coupling of up-regulation of y+ LAT2 transporter with iNOS in ammonia-exposed astrocytes may be considered a mechanism to ensure NO supply for protein nitration. This article is protected by copyright. All rights reserved.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
660925
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