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Anandamide regulates keratinocyte differentiation by inducing DNA methylation in a CB1 receptor-dependent manner
- Source :
- The Journal of biological chemistry. 283(10)
- Publication Year :
- 2008
-
Abstract
- Anandamide (arachidonoylethanolamide, AEA) belongs to an important class of endogenous lipids including amides and esters of long chain polyunsaturated fatty acids, collectively termed "endocannabinoids." Recently we have shown that AEA inhibits differentiation of human keratinocytes, by binding to type-1 cannabinoid receptors (CB1R). To further characterize the molecular mechanisms responsible for this effect, we investigated the expression of epidermal differentiation-related genes after AEA treatment. We observed that keratin 1 and 10, transglutaminase 5 and involucrin are transcriptionally down-regulated by AEA. Most importantly, we found that AEA is able to decrease differentiating gene expression by increasing DNA methylation in human keratinocytes, through a p38, and to a lesser extent p42/44, mitogen-activated protein kinase-dependent pathway triggered by CB1R. An effect of AEA on DNA methylation because of CB1R-mediated increase of methyltransferase activity is described here for the first time, and we believe that the importance of this effect clearly extends beyond the regulation of skin differentiation. In fact, the modulation of DNA methylation by endocannabinoids may affect the expression of a number of genes that regulate many cell functions in response to these substances.
- Subjects :
- Keratinocytes
Cannabinoid receptor
Methyltransferase
MAP Kinase Signaling System
Polyunsaturated Alkamides
medicine.medical_treatment
Down-Regulation
Arachidonic Acids
Biology
Biochemistry
p38 Mitogen-Activated Protein Kinases
Cell Line
chemistry.chemical_compound
Receptor, Cannabinoid, CB1
Cannabinoid Receptor Modulators
medicine
Humans
Protein Precursors
Molecular Biology
Involucrin
DNA Modification Methylases
Mitogen-Activated Protein Kinase 1
Transglutaminases
Cell Differentiation
Cell Biology
Anandamide
DNA Methylation
Keratin-10
Endocannabinoid system
chemistry
Epidermal Cells
DNA methylation
lipids (amino acids, peptides, and proteins)
Cannabinoid
Epidermis
Keratin-1
Transglutaminase 5
Endocannabinoids
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 283
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....b13ea0563543dbf288ce3e66ff0c13bf