Ceramide synthase 4 explained

Ceramide synthase 4
Symbol:CerS4
Altsymbols:LASS4
Entrezgene:79603
Hgncid:23747
Omim:615334
Refseq:NM_024552.2
Uniprot:Q9HA82
Ecnumber:2.3.1.24
Chromosome:19
Arm:p
Band:13.3

Ceramide synthase 4 (CerS4) is an enzyme that in humans is encoded by the CERS4 gene and is one of the least studied of the ceramide synthases.

Function and distribution

CerS4 synthesizes ceramides containing C18-22 fatty acids in a fumonisin B1-independent manner.[1] It is expressed at highest levels in skin, leukocytes, heart and liver, although at much lower levels than other ceramide synthases.[2]

Tissue and cellular distribution

CerS4 (TRH1) mRNA was found in all tissues and is strongly expressed in skin and muscle[1]

Clinical significance

In a 2009 study of breast cancer, total ceramide synthase levels were increased in malignant tissue, and CerS4 was one of three ceramide synthases to show an increase in mRNA levels. A significant correlation was found between CerS4 and CerS2/CerS6 expression.[3] [4] Unlike CerS1 and CerS5, CerS4 does not sensitize cells to chemotherapeutic drugs.[5]

CerS4 may also be involved in the control of body weight and food intake. Upon administration of leptin, a decrease in ceramide levels was observed in rat white adipose tissue, as were expression levels of a number of genes in the sphingolipid metabolic pathway, including CerS2 and CerS4.[6]

CerS4 expression was also found to be elevated in the brain of an Alzheimer's disease mouse model.[7]

Notes and References

  1. Riebeling C, Allegood JC, Wang E, Merrill AH, Futerman AH . Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors . Journal of Biological Chemistry . October 2003 . 278 . 44 . 43452–43459 . 10.1074/jbc.M307104200 . 12912983. free .
  2. Laviad EL, Albee L, Pankova-Kholmyansky I, Epstein S, Park H, Merrill AH, etal . Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate . Journal of Biological Chemistry . 2008 . 283 . 9 . 5677–5684 . 10.1074/jbc.M707386200 . 18165233. free .
  3. Schiffmann S, Sandner J, Birod K, Wobst I, Angioni C, Ruckhäberle E, etal . Ceramide synthases and ceramide levels are increased in breast cancer tissue . Carcinogenesis . 2009 . 30 . 5 . 745–752 . 10.1093/carcin/bgp061 . 19279183. free .
  4. Erez-Roman R, Pienik R, Futerman AH . Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression . Biochemical and Biophysical Research Communications . 2010 . 391 . 1 . 219–223 . 10.1016/j.bbrc.2009.11.035 . 19912991 .
  5. Levy M, Futerman AH . Mammalian ceramide synthases . IUBMB Life . 2010 . 62 . 5 . 347–56 . 20222015 . 10.1002/iub.319 . 2858252 .
  6. Bonzón-Kulichenko E, Schwudke D, Gallardo N, Moltó E, Fernández-Agulló T, Shevchenko A, etal . Central leptin regulates total ceramide content and sterol regulatory element binding protein-1C proteolytic maturation in rat white adipose tissue . Endocrinology . 2009 . 150 . 1 . 169–78 . 10.1210/en.2008-0505 . 18801905. free . 10115/3350 . free .
  7. Wang G, Silva J, Dasgupta S, Bieberich E . Long-chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in PS1 astrocytes . Glia . 2008 . 56 . 4 . 449–56 . 10.1002/glia.20626 . 18205190 . 5324040 .

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