Ceramide synthase 5 (CerS5) is the enzyme encoded in humans by the CERS5 gene.
Function
CerS5 robustly synthesizes C16-ceramide,[5] which is often considered to be an important pro-apoptotic ceramide.[6] De novo ceramide synthesis is an essential trigger for Bax activation in hypoxia/reoxygenation. Following hypoxia/reoxygenation, CerS5 expression is elevated. Upon knocking down acid sphingomyelinase and CerS5 in NTERA-2 cells, Bax localization to mitochondria was reduced, indicating the importance of CerS5 activity in the apoptosis pathway.[7]
Tissue distribution
CerS5 (TRH4) mRNA is found in all tissues and is strongly expressed in muscle and brain.[8] CerS5 is the major ceramide synthase detected in lung epithelia. Knock-down research in respiratory epithelium using CerS5 siRNA or fumonisin B1 reduced total CerS activity by 45% or 78%, respectively,[9] indicating that CerS5 indeed contributes significantly to ceramide synthesis in lung. In the brain, CerS5 mRNA is detected in most cells within the gray and white matter tissues.[10]
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000139624 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000023021 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ Sujoy Lahiri; Anthony H Futerman (2005). "LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor". J Biol Chem. 280 (40): 33735–8. doi:10.1074/jbc.m506485200. PMID 16100120.
- ↑ Levy M, Futerman AH (2010). "Mammalian ceramide synthases". IUBMB Life. 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252. PMID 20222015.
- ↑ Jin J, Hou Q, Mullen TD, Zeidan YH, Bielawski J, Kraveka JM, et al. (2008). "Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells". J Biol Chem. 283 (39): 26509–17. doi:10.1074/jbc.M801597200. PMC 2546549. PMID 18676372.
- ↑ Riebeling C, Allegood JC, Wang E, Merrill AH, Futerman AH (Oct 2003). "Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors". J Biol Chem. 278 (44): 43452–9. doi:10.1074/jbc.M307104200. PMID 12912983.
- ↑ Xu Z, Zhou J, McCoy DM, Mallampalli RK (2005). "LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia". J Lipid Res. 46 (6): 1229–38. doi:10.1194/jlr.M500001-JLR200. PMID 15772421.
- ↑ Becker I, Wang-Eckhardt L, Yaghootfam A, Gieselmann V, Eckhardt M (2008). "Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2". Histochem Cell Biol. 129 (2): 233–41. doi:10.1007/s00418-007-0344-0. PMID 17901973. S2CID 2595275.
- ↑ Min J, Mesika A, Sivaguru M, Van Veldhoven PP, Alexander H, Futerman AH, et al. (2007). "(Dihydro)ceramide synthase 1 regulated sensitivity to cisplatin is associated with the activation of p38 mitogen-activated protein kinase and is abrogated by sphingosine kinase 1". Mol Cancer Res. 5 (8): 801–12. doi:10.1158/1541-7786.MCR-07-0100. PMID 17699106.
- ↑ van Hall T, Wolpert EZ, van Veelen P, Laban S, van der Veer M, Roseboom M, et al. (2006). "Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants". Nat Med. 12 (4): 417–24. doi:10.1038/nm1381. PMID 16550190. S2CID 33797315.
- ↑ Panjarian S, Kozhaya L, Arayssi S, Yehia M, Bielawski J, Bielawska A, et al. (2008). "De novo N-palmitoylsphingosine synthesis is the major biochemical mechanism of ceramide accumulation following p53 up-regulation". Prostaglandins Other Lipid Mediat. 86 (1–4): 41–8. doi:10.1016/j.prostaglandins.2008.02.004. PMID 18400537.
