Evidence map›Paper›PMID 23255608›Full record

ArticleThe Journal of biological chemistry2013

Asymmetric dimethylarginine induces endothelial nitric-oxide synthase mitochondrial redistribution through the nitration-mediated activation of Akt1.

Ruslan Rafikov, Olga Rafikova, Saurabh Aggarwal, Christine Gross, Xutong Sun, Julin Desai, David Fulton, Stephen M Black

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Subcellular Localization Guides eNOS Function.International journal of molecular sciences · 2024
    Review
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  9. Inositol monophosphatase 1 as a novel interacting partner of RAGE in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2019
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Ruslan RafikovPulmonary Disease Program, Vascular Biology Center, Georgia Health Sciences University, Augusta, Georgia 30912, USA.
Olga Rafikova
Saurabh Aggarwal
Christine Gross
Xutong Sun
Julin Desai
David Fulton
Stephen M Black
Augusta University Health · US

Funding

Therapeutic Mechanisms of RhoA Inhibition In Acute Lung InjuryP01HL101902 · NHLBI · AUGUSTA UNIVERSITY · PI BLACK, STEPHEN M · 2011 to 2016
$11.2M
PERINATAL REGULATION OF THE ENDOTHELIAL NOS GENER01HL060190 · NHLBI · UNIVERSITY OF MONTANA · PI Stephen M Black · 1998 to 2026
$7.1M
ROS in Pulmonary Hypertension: Role of ADMAR01HL067841 · NHLBI · UNIVERSITY OF MONTANA · PI BLACK, STEPHEN M · 2002 to 2011
$2.6M
NHLBI NIH HHS HL101902NHLBI NIH HHS HL60190NHLBI NIH HHS HL67841NHLBI NIH HHS P01 HL101902NHLBI NIH HHS R01 HL060190NHLBI NIH HHS R01 HL067841
6 · The paper itself

Abstract

We have recently demonstrated that asymmetric dimethylarginine (ADMA) induces the translocation of endothelial nitric-oxide synthase (eNOS) to the mitochondrion via a mechanism that requires protein nitration. Thus, the goal of this study was elucidate how eNOS redistributes to mitochondria and to identify the nitrated protein responsible for this event. Our data indicate that exposure of pulmonary arterial endothelial cells to ADMA enhanced eNOS phosphorylation at the Akt1-dependent phosphorylation sites Ser(617) and Ser(1179). Mutation of these serine residues to alanine (S617A and S1179A) inhibited nitration-mediated eNOS translocation to the mitochondria, whereas the phosphormimic mutations (S617D and S1179D) exhibited increased mitochondrial redistribution in the absence of ADMA. The overexpression of a dominant-negative Akt1 also attenuated ADMA-mediated eNOS mitochondrial translocation. Furthermore, ADMA enhanced Akt1 nitration and increased its activity. Mass spectrometry identified a single nitration site in Akt1 located at the tyrosine residue (Tyr(350)) located within the client-binding domain. Replacement of Tyr(350) with phenylalanine abolished peroxynitrite-mediated eNOS translocation to mitochondria. We also found that in the absence of ADMA, eNOS translocation decreased mitochondrial oxygen consumption and superoxide production without altering cellular ATP level. This suggests that under physiologic conditions, eNOS translocation enhances mitochondria coupling. In conclusion, we have identified a new mechanism by which eNOS translocation to mitochondria is regulated by the phosphorylation of eNOS at Ser(617) and Ser(1179) by Akt1 and that this is enhanced when Akt1 becomes nitrated at Tyr(350).

Indexed as

AnimalsArginineCells, CulturedEnzyme ActivationEnzyme InhibitorsHumansMiceMitochondriaMitochondrial ProteinsNitric Oxide Synthase Type IIIOxygen ConsumptionPhosphorylationProtein TransportProto-Oncogene Proteins c-aktSheepAKT1 protein, humanAkt1 protein, mouseArginineEnzyme InhibitorsMitochondrial ProteinsNitric Oxide Synthase Type IIIN,N-dimethylarginineNOS3 protein, humanNos3 protein, mouseProto-Oncogene Proteins c-akt

Identifiers

PMID23255608
PMCPMC3585057
OpenAlexW1968959115

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.