LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia Published, JLR Papers in Press, March 16, 2005. DOI 10.1194/jlr.M500001-JLR200
By Zhiwei Xu, Jiming Zhou, D. McCoy, R. Mallampalli. 2005
50 citations recorded by the source corpus.
Ceramide is a key bioactive mediator that inhibits surfactant phosphatidylcholine (PtdCho) synthesis in lung epithelia. Ceramide availability is governed by sphingomyelin (SM) hydrolysis, but less is known regarding its de novo synthesis. In this study, we observed that ceramide synthesis within murine lung epithelia was associated with high-level ceramide synthase (dihydroceramide synthase) activity. Longevity assurance homolog 5 (LASS5) was the predominant ceramide synthase isoform detected in lung epithelia, whereas relatively lower level expression was detected for the other five mammalian homologs. Pulmonary LASS5 was developmentally regulated, but its expression was spatially and gender nonspecific. Exogenously expressed LASS5 in lung epithelia was membrane-associated, triggering increased ceramide synthesis, whereas knockdown studies using fumonisin B1 or LASS5 small, interfering RNA reduced ceramide synthase activity by 78% or 45%, respectively. Overexpression of LASS5 also reduced PtdCho synthesis, but maximal inhibition was achieved when LASS5 was coexpressed with a plasmid encoding a neutral sphingomyelinase involved in SM hydrolysis. These results demonstrate that LASS5 is the major ceramide synthase gene product involved in sphingolipid production that may also regulate PtdCho metabolism in pulmonary epithelia.
Subfields: Biochemistry, Molecular Biology, Physiology
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Citations in the corpus
- Mammalian Ceramide Synthases (2010, background): “Knockdown studies in lung epithelium using CerS5 siRNA or using fumonisin B1 reduced total CerS activity by 45% or 78%, respectively (72), demonstrating that CerS5 indeed con-”
- Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase 3 in colon cancer cells (2009, unknown): “For example, LASS5/CerS5 is important in the lung (Xu et al., 2005) and CerS6 is highly expressed in intestinal tissue (pers. comm., Dr. Anthony Futerman, Weizman Institute, Israel).”
- Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2 (2008, unknown): “Expression of CerS has been examined by Northern blot analysis and RT-PCR (Riebeling et al. 2003; Pan et al. 2001; Mizutani et al. 2005; Xu et al. 2005).”