Evidence map›Paper›PMID 25359536›Full record

ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014

Protein kinase Cδ protects against bile acid apoptosis by suppressing proapoptotic JNK and BIM pathways in human and rat hepatocytes.

Cynthia R L Webster, Andrea N Johnston, M Sawkat Anwer

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

Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Bile Acid Toxicity and Protein Kinases.Advances in experimental medicine and biology · 2021
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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.

Cynthia R L WebsterDepartment of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, Grafton, Massachusetts; cynthia.leveille-webster@tufts.edu.
Andrea N JohnstonDepartment of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, Grafton, Massachusetts;
M Sawkat AnwerDepartment of Biomedical Sciences, Cummings School of Veterinary Medicine at Tufts University, Grafton, Massachusetts.
Tufts University · US

Funding

Role of Protein Kinase C in Isoforms in Bile formation and CholestasisR01DK090010 · NIDDK · TUFTS UNIVERSITY BOSTON · PI ANWER, MOHAMMED SAWKAT · 2010 to 2014
$2.5M
cAMP modulation of bile induced hepatocyte apoptosisR01DK065975 · NIDDK · TUFTS UNIVERSITY BOSTON · PI LEVEILLE-WEBSTER, CYNTHIA R · 2005 to 2009
$1.1M
NIDDK NIH HHS R01DK065975NIDDK NIH HHS R01DK090010
6 · The paper itself

Abstract

Retained bile acids, which are capable of inducing cell death, activate protein kinase Cδ (PKC-δ) in hepatocytes. In nonhepatic cells, both pro- and antiapoptotic effects of PKC-δ are described. The aim of this study was to determine the role of PKC-δ in glycochenodeoxycholate (GCDC)-induced apoptosis in rat hepatocytes and human HUH7-Na-taurocholate-cotransporting polypeptide (Ntcp) cells. Apoptosis was monitored morphologically by Hoechst staining and biochemically by immunoblotting for caspase 3 cleavage. The role of PKC-δ was evaluated with a PKC activator (phorbol myristate acetate, PMA) and PKC inhibitors (chelerythrine, H-7, or calphostin), PKC-δ knockdown, and wild-type (WT) or constitutively active (CA) PKC-δ. PKC-δ activation was monitored by immunoblotting for PKC-δ Thr505 and Tyr311 phosphorylation or by membrane translocation. JNK and Akt phosphorylation and the amount of total bisindolylmaleimide (BIM) were determined by immunoblotting. GCDC induced the translocation of PKC-δ to the mitochondria and/or plasma membrane in rat hepatocytes and HUH7-Ntcp cells and increased PKC-δ phosphorylation on Thr505, but not on Tyr311, in HUH7-Ntcp cells. GCDC-induced apoptosis was attenuated by PMA and augmented by PKC inhibition in rat hepatocytes. In HUH-Ntcp cells, transfection with CA or WT PKC-δ attenuated GCDC-induced apoptosis, whereas knockdown of PKC-δ increased GCDC-induced apoptosis. PKC-δ silencing increased GCDC-induced JNK phosphorylation, decreased GCDC-induced Akt phosphorylation, and increased expression of BIM. GCDC translocated BIM to the mitochondria in rat hepatocytes, and knockdown of BIM in HUH7-Ntcp cells decreased GCDC-induced apoptosis. Collectively, these results suggest that PKC-δ does not mediate GCDC-induced apoptosis in hepatocytes. Instead PKC-δ activation by GCDC stimulates a cytoprotective pathway that involves JNK inhibition, Akt activation, and downregulation of BIM.

Indexed as

AnimalsApoptosisApoptosis Regulatory ProteinsBcl-2-Like Protein 11Cell MembraneGlycochenodeoxycholic AcidHepatocytesHumansJNK Mitogen-Activated Protein KinasesMembrane ProteinsMitochondriaPhosphorylationProtein Kinase C-deltaProtein TransportProto-Oncogene ProteinsRatsApoptosis Regulatory ProteinsBCL2L11 protein, humanBcl2l11 protein, ratBcl-2-Like Protein 11Glycochenodeoxycholic AcidJNK Mitogen-Activated Protein KinasesMembrane ProteinsProtein Kinase C-deltaProto-Oncogene ProteinsBCl2 proteinscell deathexchange protein activated by cAMPglycochenodeoxycholateHUH7

Identifiers

PMID25359536
PMCPMC4269680
OpenAlexW2082217975

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.