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Glucosylceramides stimulate mitogenesis in aged murine epidermis
N L Marchell1, Y Uchida, B E Brown
1Department of Veterans Affairs Medical Center and Department of Dermatology, School of Medicine, University of California, San Francisco 94121, USA.
The Journal of Investigative Dermatology
|April 16, 1998
Summary
Glucosylceramides (GlcCer) promote epidermal growth in aged mice, similar to young mice. Increasing GlcCer levels stimulates DNA synthesis and hyperplasia, without affecting stratum corneum function.
Area of Science:
- Dermatology
- Biochemistry
- Gerontology
Background:
- Glucosylceramides (GlcCer) and ceramides (Cer) have opposing roles in epidermal regulation.
- GlcCer are mitogenic in young epidermis, while Cer inhibit mitosis and induce differentiation.
Purpose of the Study:
- To investigate if GlcCer are mitogenic in aged murine epidermis.
- To explore the effects of elevated GlcCer on epidermal DNA synthesis and hyperplasia in chronologic aging.
Main Methods:
- Utilized a murine model of chronologic senescence (hairless mice up to 24 months).
- Administered topical conduritol-B epoxide (CBE) to inhibit GlcCer hydrolysis or exogenous GlcCer.
- Measured epidermal DNA synthesis via [3H]thymidine incorporation and assessed epidermal hyperplasia.
Main Results:
- Topical CBE increased epidermal DNA synthesis in all age groups, including aged mice (24 months).
- Topical GlcCer was mitogenic in both young and aged mice, showing dose and hexose specificity.
- CBE-induced DNA synthesis in aged epidermis led to hyperplasia, though absolute levels did not match younger animals.
- Stratum corneum function and membrane structure remained unchanged despite altered GlcCer levels.
Conclusions:
- Elevated endogenous GlcCer are mitogenic for both young and aged murine epidermis.
- Exogenous GlcCer, delivered via an enhancing vehicle, also demonstrates mitogenic effects.
- The mitogenic effects of increased epidermal GlcCer do not appear to be mediated by changes in stratum corneum function.