Evidence map›Paper›PMID 27253415›Full record

ArticleCell death & disease2016

Endoplasmic reticulum stress eIF2α-ATF4 pathway-mediated cyclooxygenase-2 induction regulates cadmium-induced autophagy in kidney.

B Luo, Y Lin, S Jiang, L Huang, H Yao, Q Zhuang, R Zhao, H Liu, C He, Z Lin

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

Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
6.2field-weighted citation impact, top 4% 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

44 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Cadmium toxicity and autophagy: a review.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Gut dysbacteriosis attenuates resistance toEmerging microbes & infections · 2022
    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

10 authors at 1 institution in 1 country.

B LuoState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
Y LinState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
S JiangState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
L HuangState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
H YaoState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
Q ZhuangState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
R ZhaoState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
H LiuState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
C HeState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
Z LinState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
Xiamen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The heavy metal cadmium (Cd) is nephrotoxic. Recent studies show that autophagy plays an essential role in Cd-induced kidney injury. However, the mechanisms of Cd-induced kidney injury accompanied by autophagy are still obscure. In the present study, we first confirmed that Cd induced kidney damage and dysfunction, along with autophagy, both in vivo and in vitro. Then, we observed that cyclooxygenase-2 (COX-2) and the eIF2α-ATF4 pathway of endoplasmic reticulum (ER) stress were induced by Cd in both kidney tissues and cultured cells. Further studies showed that inhibition of COX-2 with celecoxib or RNA interference (RNAi) inhibited the Cd-induced autophagy in kidney cells. In addition, blocking ER stress with 4-phenylbutyrate or RNAi partially counteracted COX-2 overexpression and autophagy induced by Cd, which suggested that ER stress was required for Cd-induced kidney autophagy. Significantly, our results showed that Cd activated ATF4 and induced its translocation to the nucleus. Knockdown of ATF4 inhibited Cd-induced COX-2 overexpression. While COX-2 overexpression is involved in renal dysfunction, there is no prior report on the role of COX-2 in autophagy regulation. The results of the current study suggest a novel molecular mechanism that the ER stress eIF2α-ATF4 pathway-mediated COX-2 overexpression contributes to Cd-induced kidney autophagy and injury. The present study implies that COX-2 may be a potential target for therapy against Cd-induced nephrotoxicity.

Indexed as

Activating Transcription Factor 4AnimalsAutophagyCadmiumCyclooxygenase 2Cyclooxygenase InhibitorsEndoplasmic Reticulum StressEnzyme InductionEukaryotic Initiation Factor-2HEK293 CellsHumansKidneyMaleMice, Inbred ICRModels, BiologicalSignal TransductionActivating Transcription Factor 4CadmiumCyclooxygenase 2Cyclooxygenase InhibitorsEukaryotic Initiation Factor-2

Identifiers

PMID27253415
PMCPMC5143407
OpenAlexW2411061174

What OpenQuestion holds

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Registered trials

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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.