Glucosylated cholesterol in skin: Synthetic role of extracellular glucocerebrosidase

Daphne E C Boer; Mina Mirzaian; Maria J Ferraz; Andreea Nadaban; Anne Schreuder; Alain Hovnanian; Jeroen van Smeden; Joke A Bouwstra; Johannes M F G Aerts

doi:10.1016/j.cca.2020.09.017

Glucosylated cholesterol in skin: Synthetic role of extracellular glucocerebrosidase

Clin Chim Acta. 2020 Nov:510:707-710. doi: 10.1016/j.cca.2020.09.017. Epub 2020 Sep 16.

Authors

Daphne E C Boer¹, Mina Mirzaian¹, Maria J Ferraz¹, Andreea Nadaban², Anne Schreuder¹, Alain Hovnanian³, Jeroen van Smeden⁴, Joke A Bouwstra², Johannes M F G Aerts⁵

Affiliations

¹ Medical Biochemistry Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
² Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
³ INSERM UMR1163, Imagine Institute, Paris Descartes University, 75015 Paris, France; Department of Genetics, Necker-Enfants Malades Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris, France.
⁴ Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands; Centre for Human Drug Research, Leiden, the Netherlands.
⁵ Medical Biochemistry Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands. Electronic address: j.m.f.g.aerts@LIC.leidenuniv.nl.

PMID: 32946792
DOI: 10.1016/j.cca.2020.09.017

Abstract

The existence of glucosylated cholesterol (GlcChol) in tissue has recently been recognized. GlcChol is generated from glucosylceramide (GlcCer) and cholesterol through transglucosylation by two retaining β-glucosidases, GBA and GBA2. Given the abundance of GBA, GlcCer and cholesterol in the skin's stratum corneum (SC), we studied the occurrence of GlcChol. A significant amount of GlcChol was detected in SC (6 pmol/mg weight). The ratio GlcChol/GlcCer is higher in SC than epidermis, 0.083 and 0.011, respectively. Examination of GlcChol in patients with Netherton syndrome revealed comparable levels (11 pmol/mg). Concluding, GlcChol was identified as a novel component in SC and is likely locally metabolized by GBA. The physiological function of GlcChol in the SC warrants future investigation.

Keywords: Glucosylated cholesterol; Stratum corneum; β-glucosidase.

MeSH terms

Cholesterol
Glucosylceramidase*
Glucosylceramides*
Humans
Skin

Substances

Glucosylceramides
Cholesterol
Glucosylceramidase