Evidence map›Paper›PMID 18660503›Full record

ArticleThe Journal of biological chemistry2008

Nerve growth factor inhibits Na+/H+ exchange and formula absorption through parallel phosphatidylinositol 3-kinase-mTOR and ERK pathways in thick ascending limb.

David W Good, Thampi George, Bruns A Watts

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
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  10. Review
  11. Epithelial transport during septic acute kidney injury.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2014
    Review
  12. Article
  13. Acute kidney injury: what part do toll-like receptors play?International journal of nephrology and renovascular disease · 2014
    Review
  14. Article
  15. A two-hit mechanism for sepsis-induced impairment of renal tubule function.American journal of physiology. Renal physiology · 2013
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
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

3 authors at 1 institution in 1 country.

David W GoodDepartments of Medicine, The University of Texas Medical Branch, Galveston, Texas 77555, USA. dgood@utmb.edu
Thampi George
Bruns A Watts
The University of Texas Medical Branch at Galveston · US

Funding

REGULATION OF THICK ASCENDING LIMB ACID-BASE TRANSPORTR01DK038217 · NIDDK · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI GOOD, DAVID WILLIAM · 1987 to 2019
$5.0M
NIDDK NIH HHS R01 DK038217NIDDK NIH HHS R01-DK-038217
6 · The paper itself

Abstract

In the medullary thick ascending limb, inhibiting the basolateral NHE1 Na(+)/H(+) exchanger with nerve growth factor (NGF) induces actin cytoskeleton remodeling that secondarily inhibits apical NHE3 and transepithelial HCO(3)(-) absorption. The inhibition by NGF is mediated 50% through activation of extracellular signal-regulated kinase (ERK). Here we examined the signaling pathway responsible for the remainder of the NGF-induced inhibition. Inhibition of HCO(3)(-) absorption was reduced 45% by the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin or LY294002 and 50% by rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), a downstream effector of PI3K. The combination of a PI3K inhibitor plus rapamycin did not cause a further reduction in the inhibition by NGF. In contrast, the combination of a PI3K inhibitor plus the MEK/ERK inhibitor U0126 completely eliminated inhibition by NGF. Rapamycin decreased NGF-induced inhibition of basolateral NHE1 by 45%. NGF induced a 2-fold increase in phosphorylation of Akt, a PI3K target linked to mTOR activation, and a 2.2-fold increase in the activity of p70 S6 kinase, a downstream effector of mTOR. p70 S6 kinase activation was blocked by wortmannin and rapamycin, consistent with PI3K, mTOR, and p70 S6 kinase in a linear pathway. Rapamycin-sensitive inhibition of NHE1 by NGF was associated with an increased level of phosphorylated mTOR in the basolateral membrane domain. These findings indicate that NGF inhibits HCO(3)(-) absorption in the medullary thick ascending limb through the parallel activation of PI3K-mTOR and ERK signaling pathways, which converge to inhibit NHE1. The results identify a role for mTOR in the regulation of Na(+)/H(+) exchange activity and implicate NHE1 as a possible downstream effector contributing to mTOR's effects on cell growth, proliferation, survival, and tumorigenesis.

Indexed as

AbsorptionAnimalsBicarbonatesCell ProliferationCells, CulturedEnzyme ActivationEnzyme InhibitorsExtracellular Signal-Regulated MAP KinasesMaleMAP Kinase Signaling SystemNerve Growth FactorPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein KinasesProto-Oncogene Proteins c-aktBicarbonatesEnzyme InhibitorsExtracellular Signal-Regulated MAP KinasesmTOR protein, ratNerve Growth FactorPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein KinasesProto-Oncogene Proteins c-aktRibosomal Protein S6 Kinases, 70-kDaSlc9a1 protein, ratSlc9a3 protein, ratSodium-Hydrogen Exchanger 1Sodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersTOR Serine-Threonine Kinases

Identifiers

PMID18660503
PMCPMC2546562
OpenAlexW1976485291

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.