uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Plasma membrane reorganization links acid sphingomyelinase/ceramide to p38 MAPK pathways in endothelial cells apoptosis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Univ Nantes, CNRS, INSERM, CRCNA, Nantes, France.. (Christer Betsholtz)
Univ Nantes, CNRS, INSERM, CRCNA, Nantes, France..
Univ Nantes, CNRS, INSERM, CRCNA, Nantes, France..
Univ Nantes, CNRS, INSERM, CRCNA, Nantes, France..
Show others and affiliations
2017 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 33, 10-21 p.Article in journal (Refereed) Published
Abstract [en]

The p38 MAPK signaling pathway is essential in the cellular response to stress stimuli, in particular in the endothelial cells that are major target of external stress. The importance of the bioactive sphingolipid ceramide generated by acid sphingomyelinase is also firmly established in stress-induced endothelial apoptotic cell death. Despite a suggested link between the p38 MAPK and ceramide pathways, the exact molecular events of this connection remain elusive. In the present study, by using two different activators of p38 MAPK, namely anisomycin and ionizing radiation, we depicted how ceramide generated by acid sphingomyelinase was involved in p38 MAPK-dependent apoptosis of endothelial cells. We first proved that both anisomycin and ionizing radiation conducted to apoptosis through activation of p38 MAPK in human microvascular endothelial cells HMEC-1. We then found that both treatments induced activation of acid sphingomyelinase and the generation of ceramide. This step was required for p38 MAPK activation and apoptosis. We finally showed that irradiation, as well as treatment with exogenous C-16-ceramide or bacterial sphingomyelinase, induced in endothelial cells a deep reorganization of the plasma membrane with formation of large lipid platforms at the cell surface, leading to p38 MAPK activation ' and apoptosis in endothelial cells. Altogether, our results proved that the plasma membrane reorganization leading to ceramide production is essential for stress-induced activation of p38 MAPK and apoptosis in endothelial cells and established the link between the acid sphingomyelinase/ceramide and p38 MAPK pathways.

Place, publisher, year, edition, pages
2017. Vol. 33, 10-21 p.
Keyword [en]
Endothelium, Stress signaling, Membrane remodeling, Ceramide p38 MAPK, Apoptosis
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-321169DOI: 10.1016/j.cellsig.2017.02.001ISI: 000397683500002PubMedID: 28179144OAI: oai:DiVA.org:uu-321169DiVA: diva2:1095297
Funder
EU, FP7, Seventh Framework Programme, 326512
Available from: 2017-05-12 Created: 2017-05-12 Last updated: 2017-05-12Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Niaudet, Colin
By organisation
Vascular Biology
In the same journal
Cellular Signalling
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 45 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf