Cited by 147Redox biology and oxidative stressCell death mechanisms and regulationGlutathione Transferases and Polymorphisms

Short interfering RNA-mediated silencing of glutaredoxin 2 increases the sensitivity of HeLa cells toward doxorubicin and phenylarsine oxide

Open access
Lillig, Christopher Horst, Lönn, Maria Elisabet, Enoksson, Mari, Fernandes, Aristi Potamitou, Holmgren, Arne·2004·Proceedings of the National Academy of Sciences

Abstract

Glutaredoxin (Grx) belongs to the thioredoxin fold superfamily and catalyzes glutathione-dependent oxidoreductions. The recently discovered mitochondrial and nuclear Grx (Grx2) differs from the more abundant cytosolic Grx (Grx1) by its higher affinity toward S -glutathionylated proteins and by being a substrate for thioredoxin reductase. Here, we have successfully established a method to silence the expression of Grx2 in HeLa cells by using short interfering RNA to study its role in the cell. Cells with levels of Grx2 <3% of the control were dramatically sensitized to cell death induced by doxorubicin/adriamycin and phenylarsine oxide but did not show signs of a general increase in oxidative damage with respect to carbonylation and glutathionylation. The ED 50 for doxorubicin dropped from 40 to 0.7 μM and for phenylarsine oxide from 200 to 5 nM. However, no differences were detected after treatment with cadmium, a known inhibitor of Grx1. These results indicate a crucial role of Grx2 in the regulation of the mitochondrial redox status and regulation of cell death at the mitochondrial checkpoint.

Integrity signals

Registry

Crossref · 10.1073/pnas.0401896101

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In cultured human cells, depletion of mitochondrial Grx2 increases cell sensitivity to apoptosis in response to agents causing oxidant stress.

    “In cultured human cells, depletion of mitochondrial Grx2 was found to increase cell sensitivity to apoptosis in response to agents causing oxidant stress (255).”

    From Redox regulation of mitochondrial function (2012) · cites this paper as [255]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Lillig, C. H., Lönn, M. E., Enoksson, M., Fernandes, A. P., & Holmgren, A.
Affiliations
Karolinska Institutet (SE)
Venue
Proceedings of the National Academy of Sciences
Published
2004-08-24
Volume
101
Issue
36
Pages
13227-13232
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2122513194
Cited by
147
References
57
Citations by year
2025: 3 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 9 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 8 · 2012: 4
FWCI
4.02
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords
glutaredoxin 2, siRNA, gene silencing, doxorubicin, phenylarsine oxide, drug sensitivity, HeLa cells, mitochondrial redox status, cell death, glutathionylation, oxidative stress, cadmium
MeSH terms
Arsenicals, Cadmium, Doxorubicin, HeLa Cells, Humans, Oxidoreductases, Oxidative Stress, Gene Silencing, RNA, Small Interfering, Glutaredoxins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review