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PMID: 11027675 Published · ppublish English Journal Article

The lipids C2- and C16-ceramide form large stable channels. Implications for apoptosis.

The Journal of biological chemistry ·Vol. 275 ·No. 49 ·2000-12-08 ·Pages 38640-4

Siskind LJ, Colombini M

Abstract

We report that physiological concentrations of both short- and long-chain ceramides, despite being lipids, form large stable pores in membranes. Some of these pores should be large enough to allow cytochrome c to permeate. Dihydroceramide differs from ceramide by the reduction of one double bond, and yet both its apoptogenic and channel-forming activities are greatly reduced. A structural model provides insight into how ceramides might form pores. According to a mathematical model, both the individual conductance of the channels and the overall membrane conductance are directly related to the overall concentration of ceramide in the membrane. Slight changes in concentration have dramatic effects on the size of the channels formed, providing an easy way for rapidly altering membrane permeability by changing the activity of local synthetic and catabolic enzymes. A possible role for these channels in apoptosis is discussed.

MeSH Terms
Apoptosis Ceramides/chemistry Cholesterol/chemistry Electric Conductivity Electrochemistry Ion Channels Liposomes/chemistry Models, Biological Models, Molecular Molecular Conformation Phosphatidylcholines Phospholipids/chemistry Sphingosine/analogs & derivatives,chemistry Structure-Activity Relationship
Chemicals
Ceramides Ion Channels Liposomes N-acetylsphingosine Phosphatidylcholines Phospholipids N-palmitoylsphingosine asolectin Cholesterol Sphingosine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Siskind L J
Department of Biology, University of Maryland College Park, College Park, Maryland 20742, USA.
Colombini M
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.C000587200
Published
2000-12-08
Pages
38640-4
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2094390
Subset
IM
Grants
NINDS NIH HHS · F31 NS042467 · United States
NINDS NIH HHS · F31 NS042467-01 · United States
External Links
PubMed source DOI: 10.1074/jbc.C000587200 PMC Full Text View journal details
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