Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26943326
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Nitro-Arachidonic Acid Prevents Angiotensin II-Induced Mitochondrial Dysfunction
in a Cell Line of Kidney Proximal Tubular Cells
#MMPMID26943326
Sánchez-Calvo B
; Cassina A
; Rios N
; Peluffo G
; Boggia J
; Radi R
; Rubbo H
; Trostchansky A
PLoS One
2016[]; 11
(3
): e0150459
PMID26943326
show ga
Nitro-arachidonic acid (NO2-AA) is a cell signaling nitroalkene that exerts
anti-inflammatory activities during macrophage activation. While angiotensin II
(ANG II) produces an increase in reactive oxygen species (ROS) production and
mitochondrial dysfunction in renal tubular cells, little is known regarding the
potential protective effects of NO2-AA in ANG II-mediated kidney injury. As such,
this study examines the impact of NO2-AA on ANG II-induced mitochondrial
dysfunction in an immortalized renal proximal tubule cell line (HK-2 cells).
Treatment of HK-2 cells with ANG II increases the production of superoxide
(O2?-), nitric oxide (?NO), inducible nitric oxide synthase (NOS2) expression,
peroxynitrite (ONOO-) and mitochondrial dysfunction. Using high-resolution
respirometry, it was observed that the presence of NO2-AA prevented ANG
II-mediated mitochondrial dysfunction. Attempting to address mechanism, we
treated isolated rat kidney mitochondria with ONOO-, a key mediator of ANG
II-induced mitochondrial damage, in the presence or absence of NO2-AA. Whereas
the activity of succinate dehydrogenase (SDH) and ATP synthase (ATPase) were
diminished upon exposure to ONOO-, they were restored by pre-incubating the
mitochondria with NO2-AA. Moreover, NO2-AA prevents oxidation and nitration of
mitochondrial proteins. Combined, these data demonstrate that ANG II-mediated
oxidative damage and mitochondrial dysfunction is abrogated by NO2-AA,
identifying this compound as a promising pharmacological tool to prevent ANG
II-induced renal disease.
free
free
free
