Glycerophospholipid profile in oncogene-induced senescence

Cristina Cadenas, Sonja Vosbeck, Eva Maria Hein, Birte Hellwig, Alice Langer, Heiko Hayen, Dennis Franckenstein, Bettina Büttner, Seddik Hammad, Rosemarie Marchan, Matthias Hermes, Silvia Selinski, Jörg Rahnenführer, Begüm Peksel, Zsolt Török, László Vígh, Jan G. Hengstler

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Alterations in lipid metabolism and in the lipid composition of cellular membranes are linked to the pathology of numerous diseases including cancer. However, the influence of oncogene expression on cellular lipid profile is currently unknown. In this work we analyzed changes in lipid profiles that are induced in the course of ERBB2-expression mediated premature senescence. As a model system we used MCF-7 breast cancer cells with doxycycline-inducible expression of NeuT, an oncogenic ERBB2 variant. Affymetrix gene array data showed NeuT-induced alterations in the transcription of many enzymes involved in lipid metabolism, several of which (ACSL3, CHPT1, PLD1, LIPG, MGLL, LDL and NPC1) could be confirmed by quantitative realtime PCR. A study of the glycerophospholipid and lyso-glycerophospholipid profiles, obtained by high performance liquid chromatography coupled to Fourier-transform ion cyclotron resonance-mass spectrometry revealed senescence-associated changes in numerous lipid species, including mitochondrial lipids. The most prominent changes were found in PG(34:1), PG(36:1) (increased) and LPE(18:1), PG(40:7) and PI(36:1) (decreased). Statistical analysis revealed a general trend towards shortened phospholipid acyl chains in senescence and a significant trend to more saturated acyl chains in the class of phosphatidylglycerol. Additionally, the cellular cholesterol content was elevated and accumulated in vacuoles in senescent cells. These changes were accompanied by increased membrane fluidity. In mitochondria, loss of membrane potential along with altered intracellular distribution was observed. In conclusion, we present a comprehensive overview of altered cholesterol and glycerophospholipid patterns in senescence, showing that predominantly mitochondrial lipids are affected and lipid species less susceptible to peroxidation are increased.

Original languageEnglish
Pages (from-to)1256-1268
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1821
Issue number9
DOIs
Publication statusPublished - Sep 1 2012

Keywords

  • Cholesterol
  • ERBB2
  • Glycerolipids
  • Membrane fluidity
  • Mitochondria
  • Senescence

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Cadenas, C., Vosbeck, S., Hein, E. M., Hellwig, B., Langer, A., Hayen, H., Franckenstein, D., Büttner, B., Hammad, S., Marchan, R., Hermes, M., Selinski, S., Rahnenführer, J., Peksel, B., Török, Z., Vígh, L., & Hengstler, J. G. (2012). Glycerophospholipid profile in oncogene-induced senescence. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1821(9), 1256-1268. https://doi.org/10.1016/j.bbalip.2011.11.008