Evidence map›Paper›PMID 20053794›Full record

ArticleAmerican journal of physiology. Renal physiology2010

PKC-alpha mediates flow-stimulated superoxide production in thick ascending limbs.

Nancy J Hong, Guillermo B Silva, Jeffrey L Garvin

Abstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Review
  3. Angiotensin II acts through Rac1 to upregulate pendrin: role of NADPH oxidase.American journal of physiology. Renal physiology · 2024
    Article
  4. Dietary fructose enhances angiotensin II-stimulated NaAmerican journal of physiology. Renal physiology · 2020
    Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Oxidant Mechanisms in Renal Injury and Disease.Antioxidants & redox signaling · 2016
    Review
  10. Article
  11. Article
  12. Shear stress blunts tubuloglomerular feedback partially mediated by primary cilia and nitric oxide at the macula densa.American journal of physiology. Regulatory, integrative and comparative physiology · 2015
    Article
  13. Article
  14. Article
  15. Endothelial actin depolymerization mediates NADPH oxidase-superoxide production during flow reversal.American journal of physiology. Heart and circulatory physiology · 2014
    Article
  16. Oxidative stress in hypertension: role of the kidney.Antioxidants & redox signaling · 2014
    Review
  17. NADPH oxidases, reactive oxygen species, and the kidney: friend and foe.Journal of the American Society of Nephrology : JASN · 2013
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Nancy J HongDepartment of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, USA.
Guillermo B Silva
Jeffrey L Garvin
Henry Ford Hospital · USWayne State University · US

Funding

VASOACTIVE HORMONES IN THE REGULATION OF BLOOD PRESSUREP01HL028982 · NHLBI · HENRY FORD HOSPITAL · PI ORTIZ, PABLO A. · 1985 to 2017
$39.8M
Tubuloglomerular Feedback Regulation by Carbon MonoxideP01HL090550 · NHLBI · HENRY FORD HEALTH SYSTEM · PI ORTIZ, PABLO A. · 2009 to 2013
$10.2M
Salt-Sensitive Hypertension: Role of Renal SuperoxideR01HL070985 · NHLBI · HENRY FORD HEALTH SYSTEM · PI Jeffrey L. Garvin · 2002 to 2026
$6.3M
NHLBI NIH HHS HL-28982NHLBI NIH HHS HL-70985NHLBI NIH HHS HL-90550NHLBI NIH HHS R01 HL070985
6 · The paper itself

Abstract

We showed that luminal flow increases net superoxide (O(2)(-)) production via NADPH oxidase in thick ascending limbs. Protein kinase C (PKC) activates NADPH oxidase activity in phagocytes, cardiomyocytes, aortic endothelial cells, vascular smooth muscle cells, and renal mesangial cells. However, the flow-activated pathway that induces NADPH oxidase activity in thick ascending limbs is unclear. We hypothesized that PKC mediates flow-stimulated net O(2)(-) production by thick ascending limbs. Initiation of flow (20 nl/min) increased net O(2)(-) production from 4 +/- 1 to 61 +/- 12 AU/s (P < 0.007; n = 5). The NADPH oxidase inhibitor apocynin completely blocked the flow-induced increase in net O(2)(-) production (2 +/- 1 vs. 1 +/- 1 AU/s; P > 0.05; n = 5). Flow-stimulated O(2)(-) was also blocked in p47(phox)-deficient mice. We measured flow-stimulated PKC activity with a fluorescence resonance energy transfer (FRET)-based membrane-targeted PKC activity reporter and found that the FRET ratio increased from 0.87 +/- 0.02 to 0.96 +/- 0.04 AU (P < 0.05; n = 6). In the absence of flow, the PKC activator phorbol 12-myristate 13-acetate (200 nM) enhanced net O(2)(-) production from 5 +/- 2 to 92 +/- 6 AU/s (P < 0.001; n = 6). The PKC-alpha- and betaI-selective inhibitor Gö 6976 (100 nM) decreased flow-stimulated net O(2)(-) production from 54 +/- 15 to 2 +/- 1 AU/s (P < 0.04; n = 5). Flow-induced net O(2)(-) production was inhibited in thick ascending limbs transduced with dominant-negative (dn)PKC-alpha but not dnPKCbetaI or LacZ (Delta = 11 +/- 3 AU/s for dnPKCalpha, 55 +/- 7 AU/s for dnPKCbetaI, and 63 +/- 7 AU/s for LacZ; P < 0.001; n = 6). We concluded that flow stimulates net O(2)(-) production in thick ascending limbs via PKC-alpha-mediated activation of NADPH oxidase.

Indexed as

AnimalsGene Expression Regulation, EnzymologicIsoenzymesKidney MedullaLoop of HenleMaleMiceMice, Inbred C57BLNADPH OxidasesProtein Kinase CProtein Kinase C-alphaProtein Kinase C betaRatsRats, Sprague-DawleySuperoxidesIsoenzymesNADPH Oxidasesneutrophil cytosolic factor 1Protein Kinase CProtein Kinase C-alphaProtein Kinase C betaSuperoxides

Identifiers

PMID20053794
PMCPMC2853312
OpenAlexW1982578656

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.