Evidence map›Paper›PMID 26935704›Full record

ArticleInternational journal of molecular medicine2016

Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: A mechanism for uric acid-induced endothelial dysfunction.

Peng Li, Lina Zhang, Mei Zhang, Changyong Zhou, Nan Lin

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

Article in International journal of molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 3 pooled it
8.2field-weighted citation impact, top 2% 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

88 citing papers in PubMed, 3 syntheses or guidelines pooled it, 147 citations in OpenAlex.

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28 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Peng LiThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministy of Education and Chinese Ministy of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
Lina ZhangDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China.
Mei ZhangThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministy of Education and Chinese Ministy of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.
Changyong ZhouDepartment of Emergency Room, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China.
Nan LinDepartment of Emergency Room, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China.
Qingdao University · CNQilu Hospital of Shandong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mechanism by which hyperuricemia induced-endothelial dysfunction contributes to cardiovascular diseases (CVDs) is not yet fully understood. In the present study, we used uric acid (UA) to trigger endothelial dysfunction in cultured endothelial cells, and investigated the effects of induced reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress induction, and the protein kinase C (PKC)-dependent endothelial nitric oxide synthase (eNOS) signaling pathway. Human umbilical vein endothelial cells (HUVECs) were incubated with 6, 9 or 12 mg/dl UA, ROS scavenger polyethylene glycol-superoxide dismutase (PEG‑SOD), ER stress inhibitor 4-phenylbutyric acid (4-PBA), and PKC inhibitor polymyxin B for 6-48 h. Nitric oxide (NO) production, eNOS activity, intracellular ROS, ER stress levels, and the interaction between eNOS and calmodulin (CaM) and cytosolic calcium levels were assessed using fluorescence microscopy and western blot analysis. Apoptosis was assessed by annexin V staining. UA increased HUVEC apoptosis and reduced eNOS activity and NO production in a dose- and time-dependent manner. Intracellular ROS was elevated after 3 h, while ER stress level increased after 6 h. UA did not alter intracellular Ca2+, CaM, or eNOS concentration, or eNOS Ser1177 phosphorylation. However, PKC-dependent eNOS phosphorylation at Thr495 was greatly enhanced, and consequently interaction between eNOS and CaM was reduced. Cellular ROS depletion, ER stress inhibition and PKC activity reduction inhibited the effect of UA on eNOS activity, NO release and apoptosis in HUVECs. Thus, we concluded that UA induced HUVEC apoptosis and endothelial dysfunction by triggering oxidative and ER stress through PKC/eNOS-mediated eNOS activity and NO production.

Indexed as

Endoplasmic Reticulum StressApoptosisEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsNitric OxideNitric Oxide Synthase Type IIIOxidative StressPhosphorylationPolyethylene GlycolsProtein Kinase CReactive Oxygen SpeciesSuperoxide DismutaseUric AcidNitric OxideNitric Oxide Synthase Type IIIPolyethylene Glycolspolyethylene glycol-superoxide dismutaseProtein Kinase CReactive Oxygen SpeciesSuperoxide DismutaseUric Acid

Identifiers

PMID26935704
PMCPMC4790645
OpenAlexW2286689220

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.