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Cholesterol sulfate and calcium affect stratum corneum lipid organization over a wide temperature range.
J Lipid Res. 1999 Dec; 40(12):2303-12.JL

Abstract

The main diffusion barrier for drugs penetrating through the skin is located in the intercellular lipid matrix in the upper layer of the skin, the stratum corneum (SC). The main lipid classes in the SC are ceramides (CER), free fatty acids (FFA) and cholesterol (CHOL). The lipids in SC are organized into two lamellar phases with periodicities of approximately 13 and 6 nm, respectively. Similar lipid organization has been found with equimolar CHOL:CER:FFA mixtures in SAXD studies performed at room temperature. However, one may conclude that the phase behavior of the mixtures is similar to that in SC only when the lipid organization of the lipid mixtures resembles that in SC over a wide temperature range. Therefore, in the present study, the organization of the lipid mixtures has been studied in a temperature range between 20 degrees and 95 degrees C. From these experiments it appeared that at elevated temperatures in equimolar CHOL:CER:FFA mixtures a new prominent 4.3 nm phase is formed between 35;-55 degrees C, which is absent or only weakly formed in intact human and pig SC, respectively. As it has been suggested that gradients of pH and cholesterol sulfate exist in the SC and that Ca(2+) is present only in the lowest SC layers, the effect of pH, cholesterol sulfate, and Ca(2+) on the lipid phase behavior has been investigated with lipid mixtures. Both an increase in pH from 5 (pH at the skin surface) to 7.4 (pH at the SC;-stratum granulosum interface) and the presence of cholesterol sulfate promote the formation of the 13 nm lamellar phase. Furthermore, cholesterol sulfate reduces the amount of CHOL that is present in crystalline domains, causes a shift in the formation of the 4.3 nm phase to higher temperatures, and makes this phase less prominent at higher temperatures. The finding that Ca(2+) counteracts the effects of cholesterol sulfate indicates the importance of a proper balance of minor SC components for appropriate SC lipid organization. In addition, when the findings are extrapolated to the in vivo situation, it seems that cholesterol sulfate is required to dissolve cholesterol in the lamellar phases and to stabilize SC lipid organization. Therefore, a drop in cholesterol sulfate content in the superficial layers of the SC is expected to destabilize the lipid lamellar phases, which might facilitate the desquamation process.

Authors+Show Affiliations

Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10588956

Citation

Bouwstra, J A., et al. "Cholesterol Sulfate and Calcium Affect Stratum Corneum Lipid Organization Over a Wide Temperature Range." Journal of Lipid Research, vol. 40, no. 12, 1999, pp. 2303-12.
Bouwstra JA, Gooris GS, Dubbelaar FE, et al. Cholesterol sulfate and calcium affect stratum corneum lipid organization over a wide temperature range. J Lipid Res. 1999;40(12):2303-12.
Bouwstra, J. A., Gooris, G. S., Dubbelaar, F. E., & Ponec, M. (1999). Cholesterol sulfate and calcium affect stratum corneum lipid organization over a wide temperature range. Journal of Lipid Research, 40(12), 2303-12.
Bouwstra JA, et al. Cholesterol Sulfate and Calcium Affect Stratum Corneum Lipid Organization Over a Wide Temperature Range. J Lipid Res. 1999;40(12):2303-12. PubMed PMID: 10588956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cholesterol sulfate and calcium affect stratum corneum lipid organization over a wide temperature range. AU - Bouwstra,J A, AU - Gooris,G S, AU - Dubbelaar,F E, AU - Ponec,M, PY - 1999/12/10/pubmed PY - 1999/12/10/medline PY - 1999/12/10/entrez SP - 2303 EP - 12 JF - Journal of lipid research JO - J Lipid Res VL - 40 IS - 12 N2 - The main diffusion barrier for drugs penetrating through the skin is located in the intercellular lipid matrix in the upper layer of the skin, the stratum corneum (SC). The main lipid classes in the SC are ceramides (CER), free fatty acids (FFA) and cholesterol (CHOL). The lipids in SC are organized into two lamellar phases with periodicities of approximately 13 and 6 nm, respectively. Similar lipid organization has been found with equimolar CHOL:CER:FFA mixtures in SAXD studies performed at room temperature. However, one may conclude that the phase behavior of the mixtures is similar to that in SC only when the lipid organization of the lipid mixtures resembles that in SC over a wide temperature range. Therefore, in the present study, the organization of the lipid mixtures has been studied in a temperature range between 20 degrees and 95 degrees C. From these experiments it appeared that at elevated temperatures in equimolar CHOL:CER:FFA mixtures a new prominent 4.3 nm phase is formed between 35;-55 degrees C, which is absent or only weakly formed in intact human and pig SC, respectively. As it has been suggested that gradients of pH and cholesterol sulfate exist in the SC and that Ca(2+) is present only in the lowest SC layers, the effect of pH, cholesterol sulfate, and Ca(2+) on the lipid phase behavior has been investigated with lipid mixtures. Both an increase in pH from 5 (pH at the skin surface) to 7.4 (pH at the SC;-stratum granulosum interface) and the presence of cholesterol sulfate promote the formation of the 13 nm lamellar phase. Furthermore, cholesterol sulfate reduces the amount of CHOL that is present in crystalline domains, causes a shift in the formation of the 4.3 nm phase to higher temperatures, and makes this phase less prominent at higher temperatures. The finding that Ca(2+) counteracts the effects of cholesterol sulfate indicates the importance of a proper balance of minor SC components for appropriate SC lipid organization. In addition, when the findings are extrapolated to the in vivo situation, it seems that cholesterol sulfate is required to dissolve cholesterol in the lamellar phases and to stabilize SC lipid organization. Therefore, a drop in cholesterol sulfate content in the superficial layers of the SC is expected to destabilize the lipid lamellar phases, which might facilitate the desquamation process. SN - 0022-2275 UR - https://www.unboundmedicine.com/medline/citation/10588956/Cholesterol_sulfate_and_calcium_affect_stratum_corneum_lipid_organization_over_a_wide_temperature_range_ L2 - http://www.jlr.org/cgi/pmidlookup?view=long&pmid=10588956 DB - PRIME DP - Unbound Medicine ER -