A shift in sphingolipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells
Open accessAbstract
Sphingolipids, major lipid components of the eukaryotic plasma membrane, have a variety of physiological functions and have been associated with many diseases. They have also been implicated in apoptosis. Sphingolipids are heterogeneous in their acyl chain length, with long-chain (C16) and very long-chain (C24) sphingolipids being predominant in most mammalian tissues. We demonstrate that knockdown of ELOVL1 or CERS2, which catalyze synthesis of C24 acyl-CoAs and C24 ceramide, respectively, drastically reduced C24 sphingolipid levels with a complementary increase in C16 sphingolipids. Under ELOVL1 or CERS2 knockdown conditions, cisplatin-induced apoptosis significantly increased. Enhanced sensitivity to cisplatin-induced apoptosis exhibited close correlation with increases in caspase-3/7 activity. No significant alterations in sphingolipid metabolism such as ceramide generation were apparent with the cisplatin-induced apoptosis, and inhibitors of ceramide generation had no effect on the apoptosis. Apoptosis induced by UV radiation or C6 ceramides also increased in ELOVL1 or CERS2 knockdown cells. Changes in the composition of sphingolipid chain length may affect susceptibility to stimuli-induced apoptosis by affecting the properties of cell membranes, such as lipid microdomain/raft formation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
VLCFAs increase membrane stiffness, thereby decreasing fluidity, and are likely critical for proper myelin function, myelination, myelin maintenance, and neuron polarity during CNS development.
“VLCFAs increase membrane stiffness, thereby decreasing fluidity, and they are likely critical for proper myelin function [191,213,214,217], myelination [218], myelin maintenance [207,213,215], and neuron polarity during CNS development [219].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [214]
The Discussion (page unavailable) reports that membrane vesicles from mice deficient in C24 sphingolipids had increased fluidity, supporting the membrane-fluidity point. It also links VLCFA accumulation in X-linked adrenoleukodystrophy to progressive demyelination, but does not establish that VLCFAs are critical for proper myelin function. The separate claims about myelination, maintenance, and neuron polarity have other citations in the citing sentence. (LLM, conf=0.78)
Experimental — accuracy not yet measuredHalf of myelin sphingolipids contain VLCFAs (C > 22).
“Half of myelin sphingolipids contain VLCFAs (C > 22) [213,214,215].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [214]
The Introduction (page unavailable) says that C24 sphingolipids contain very-long-chain fatty acids, but gives no proportion for myelin sphingolipids. A search for myelin and for a half-or-50% figure found no passage establishing the claimed proportion. (LLM, conf=0.74)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 36 · Cited by 102
- Authors
- Sassa, T., Suto, S., Okayasu, Y., & Kihara, A.
- Affiliations
- Hokkaido University (JP)
- Corresponding author
- Kihara, Akio
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 1821
- Issue
- 7
- Pages
- 1031-1037
- ISSN
- 1388-1981 (ISSN-L)
- OpenAlex
- W2162114124
- Cited by
- 102
- References
- 36
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 12 · 2021: 10 · 2020: 8 · 2019: 15 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 9 · 2014: 7 · 2013: 3 · 2012: 3
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (JSPS) (23370057)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- sphingolipids, ELOVL1, ceramide synthase 2, cisplatin-induced apoptosis, caspase-3/7 activation, UV-induced apoptosis, C6-ceramide, ceramide generation, lipid rafts, HeLa cells, sphingolipid metabolism
- MeSH terms
- Fatty Acid Elongases, Acetyltransferases, Ceramides, Cisplatin, Colorimetry, HeLa Cells, Humans, Membrane Proteins, Transfection, Ultraviolet Rays, Apoptosis, Membrane Microdomains, Tumor Suppressor Proteins, RNA, Small Interfering, Lipid Metabolism, Sphingosine N-Acyltransferase, Caspase 3, Caspase 7, Gene Knockdown Techniques
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
