Evidence map›Paper›PMID 25679868›Full record

ArticleEndocrinology2015

Role of Ca(2+)/calmodulin-dependent protein kinase kinase in adrenal aldosterone production.

Kazutaka Nanba, Andrew Chen, Koshiro Nishimoto, William E Rainey

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Somatic Mutations inHypertension (Dallas, Tex. : 1979) · 2025
    Article
  2. Article
  3. Review
  4. Molecular Mechanisms Underlying CaInternational journal of molecular sciences · 2022
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. MMolecular and cellular endocrinology · 2018
    Article
  11. Article
  12. Article
  13. Age-dependent Increases in Adrenal Cytochrome b5 and Serum 5-Androstenediol-3-sulfate.The Journal of clinical endocrinology and metabolism · 2016
    Article
  14. Article
  15. Review
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

4 authors at 1 institution in 1 country.

Kazutaka NanbaDepartment of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
Andrew Chen
Koshiro Nishimoto
William E Rainey
University of Michigan–Ann Arbor · US

Funding

MECHANISMS LEADING TO ADRENAL ZONATIONR01DK043140 · NIDDK · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI William E Rainey · 1999 to 2026
$7.2M
MECHANISMS LEADING TO ADRENAL ZONATIONR29DK043140 · NIDDK · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI RAINEY, WILLIAM E · 1994 to 1998
–
NIDDK NIH HHS DK43140NIDDK NIH HHS R01 DK043140
6 · The paper itself

Abstract

There is considerable evidence supporting the role of calcium signaling in adrenal regulation of both aldosterone synthase (CYP11B2) and aldosterone production. However, there have been no studies that investigated the role played by the Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) in adrenal cells. In this study we investigated the role of CaMKK in adrenal cell aldosterone production. To determine the role of CaMKK, we used a selective CaMKK inhibitor (STO-609) in the HAC15 human adrenal cell line. Cells were treated with angiotensin II (Ang II) or K+ and evaluated for the expression of steroidogenic acute regulatory protein and CYP11B2 (mRNA/protein) as well as aldosterone production. We also transduced HAC15 cells with lentiviral short hairpin RNAs of CaMKK1 and CaMKK2 to determine which CaMKK plays a more important role in adrenal cell regulation of the calcium signaling cascade. The CaMKK inhibitor, STO-609, decreased aldosterone production in cells treated with Ang II or K+ in a dose-dependent manner. STO-609 (20 μM) also inhibited steroidogenic acute regulatory protein and CYP11B2 mRNA/protein induction. CaMKK2 knockdown cells showed significant reduction of CYP11B2 mRNA induction and aldosterone production in cells treated with Ang II, although there was no obvious effect in CaMKK1 knockdown cells. In immunohistochemical analysis, CaMKK2 protein was highly expressed in human adrenal zona glomerulosa with lower expression in the zona fasciculata. In conclusion, the present study suggests that CaMKK2 plays a pivotal role in the calcium signaling cascade regulating adrenal aldosterone production.

Indexed as

Adrenal CortexAldosteroneAngiotensin IIBenzimidazolesCalcium-Calmodulin-Dependent Protein Kinase KinaseCell LineCytochrome P-450 CYP11B2Gene Knockdown TechniquesHumansNaphthalimidesPhosphoproteinsPotassiumReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSignal TransductionAldosteroneAngiotensin IIBenzimidazolesCalcium-Calmodulin-Dependent Protein Kinase KinaseCAMKK1 protein, humanCAMKK2 protein, humanCytochrome P-450 CYP11B2NaphthalimidesPhosphoproteinsPotassiumRNA, MessengerRNA, Small InterferingSteroidogenic Acute Regulatory ProteinSTO 609Vasoconstrictor Agents

Identifiers

PMID25679868
PMCPMC4398758
OpenAlexW2062971730

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.