Glucosylceramides stimulate mitogenesis in aged murine epidermis

The Journal of Investigative Dermatology
N L MarchellW M Holleran

Abstract

Glucosylceramides (GlcCer) and ceramides (Cer) appear to have opposite effects on epidermal growth and differentiation. Whereas Cer inhibit mitosis and induce terminal differentiation and apoptosis in cultured keratinocytes, GlcCer is mitogenic in young murine epidermis. Using a recently described murine model of chronologic senescence we explored whether GlcCer is mitogenic in aged epidermis. Epidermal GlcCer content increases following topical applications of either conduritol-B epoxide (CBE), an inhibitor of GlcCer hydrolysis, or exogenous GlcCer in a penetration-enhancing vehicle. During chronologic aging in the hairless mouse, baseline epidermal DNA synthesis rates remain normal until 18 mo, but decline significantly at 24 mo. Topical CBE stimulates a 1.5- to 1.9-fold increase in epidermal DNA synthesis in all age groups (i.e., 1-2, 18, and 24 mo). Although the CBE induced increase in [3H]thymidine incorporation in 24 mo old animals is significant (p < 0.01), it is not sufficient to reach the absolute levels reached in similarly treated, younger mouse epidermis. Moreover, topical GlcCer induced mitogenesis is both dose dependent and hexose specific in young (1-2 mo old) animals, and remains effective in aged (< or = 24 mo ...Continue Reading

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Citations

Jun 30, 2004·Blood Cells, Molecules & Diseases·Selena Trajkovic-BodennecAnthony H Futerman
Jun 20, 2002·The Journal of Biological Chemistry·Kate J ClaycombeSimin Nikbin Meydani
Oct 21, 2009·Cell Biochemistry and Function·Mark E Venable, Xinhe Yin
Sep 12, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jacques BodennecAnthony H Futerman
Jan 1, 2013·Biomolecules·Paulette M TamashiroToshihiko Kawamori
May 29, 2016·The Journal of Pathology·Ayelet VardiAnthony H Futerman
Jun 1, 2000·Biochimica Et Biophysica Acta·A HuwilerK Sandhoff
Mar 27, 2002·Clinics in Geriatric Medicine·Peter M Elias, Ruby Ghadially
Feb 13, 2018·Journal of Proteome Research·Pierre Le PogamDavid Rondeau

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