Ceramides--Friend or Foe in Hypoxia?

CM Crowder - Science, 2009 - science.org
Science, 2009science.org
PERSPECTIVES cells, and deletion of LAG1 increases the life span of haploid yeast cells,
suggesting a role for this synthase in cellular aging (5). Expression of wild-type hyl-2 in yeast
cells lacking both LAG1 and LAC1 genes restored yeast viability, indicating that hyl-2
encodes an authentic ceramide synthase. Ceramide synthases acylate sphingoid bases
with different lengths of fatty acid chains, ranging from 14 to 26 carbon atoms, to produce a
family of ceramides (6). Ceramides serve as intermediates for sphingolipids, a major …
PERSPECTIVES cells, and deletion of LAG1 increases the life span of haploid yeast cells, suggesting a role for this synthase in cellular aging (5). Expression of wild-type hyl-2 in yeast cells lacking both LAG1 and LAC1 genes restored yeast viability, indicating that hyl-2 encodes an authentic ceramide synthase. Ceramide synthases acylate sphingoid bases with different lengths of fatty acid chains, ranging from 14 to 26 carbon atoms, to produce a family of ceramides (6). Ceramides serve as intermediates for sphingolipids, a major component of cell membranes. Beyond their structural role, ceramides have been implicated as signaling molecules in diverse biological processes in mammalian cells including inflammation, cellular differentiation, and cellular stress responses (7–10). In response to various stresses such as hypoxia and restricted blood supply (ischemia), total cellular ceramide concentration increases, which in turn can activate molecules that induce cell death (apoptosis)(7, 11). ButC. eleganshas two other ceramide synthase gene homologs, hyl-1 and lagr-1. Both hyl-1 and lagr-1 are required for radiationinduced apoptosis, and germline injection of the 16-carbon ceramide can restore germline apoptosis in a hyl-1 or lagr-1 deletion mutant (12). Thus, ceramide (at least the 16-carbon ceramide) appears to promote radiationinduced germline apoptosis in C. elegans.
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