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Chapter 6 Cholesterol Metabolism in the Epidermis

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Abstract

“Cholesterol is good for your skin” may be an improbable headline that you would see in a health magazine—but it is the reality. Cholesterol is required to form membranes in cells and is also crucial for the formation of the extracellular lamellae in the stratum corneum that provides the permeability barrier for the skin. Keratinocytes in the epidermis, as they stratify and differentiate, synthesize a variety of structural proteins (primarily keratins but also the proteins that form the cornified envelope such as involucrin and loricrin) as well as lipids which are packaged in secretory organelles termed as the epidermal lamellar bodies (LBs).

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References

  • Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res. 1991;24:1–26.

    Google Scholar 

  • Elias PM, Williams ML, Maloney ME, Bonifas JA, Brown BE, Grayson S, Epstein EH Jr. Stratum corneum lipids in disorders of cornification. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis. J Clin Invest. 1984;74:1414–21.

    Google Scholar 

  • Elias PM, Crumrine D, Rassner U, Hachem J-P, Menon GK, Man AW, Choi MH, Leypold L, ­Feingold KR, Williams ML. Basic of abnormal desquamation and permeability barrier ­dysfunction in RXLI. J. Invest. Dermatol. 2004;122:314–319.

    Google Scholar 

  • Elias PM, Williams ML, Choi E-U, Feingold KR. Role of cholesterol sulfate in epidermal structure and function: lessons from X-linked ichthyosis. Biochem Biophys Acta Mol Cell Biol Lipids. 2014;1841(3):353–61.

    Google Scholar 

  • Epstein EH, Williams ML, Elias PM. The epidermal cholesterol sulfate cycle. J Am Acad Dermatol. 1984;10:866–8.

    Google Scholar 

  • Feingold KR, Wiley MH, MacRae G, Lear S, Moser AH, Zsigmond G, Siperstein MD. Denovo sterologenesis in the intact rat. Metabolism. 1983;32:75–81.

    Google Scholar 

  • Feingold KR. The regulation and role of epidermal lipid synthesis. Adv Lipid Res. 1991;24:57–82.

    Google Scholar 

  • Feingold KRE, Man MQ, Menon GK, Cho SS, Brown BE, Elias PM. Cholesterolsynthesis is required for cutaneous barrier function in mice. J Clin Invest. 1990;86:1738–45.

    Google Scholar 

  • Feingold KR, Man MQ, Proksch E, Menon GK, Brown BE, Elias PM. The lovastatin-treated rodent: a new model of barrier disruption and epidermal hyperplasia. J Invest Dermatol. 1991;96:201–9.

    Google Scholar 

  • Ghadially R, Brown BE, Sequeira-Martin SM, Feingold KR, Elias PM. The aged epidermal permeability barrier. Structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model. J Clin Invest. 1995;95:2281–90.

    Google Scholar 

  • Grayson S, Johnson-Vinegar AG, Wintraub BU, Isserhoff RR, Epstein EH, Jr, Elias PM. Lamellar body-enriched fractions from neonatal mice: preparative techniques and partial characterization. J. Invest. Dermatol. 1985;85:289–294.

    Google Scholar 

  • Hachem JP, Crumrine D, Fluhr J, Brown BE, Feingold KR, Elias PM. pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. J Invest Dermatol. 2003;121:345–53.

    Google Scholar 

  • Hachem JP, Wagberg F, Schmuth M, et al. Serine protease activity and residual LEKTI expression determine phenotype in Netherton Syndrome. J. Invest. Dermatol. 2006;126:1609–1621.

    Google Scholar 

  • Hanley K, Wood L, Ng DC, et al. Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D. J Lipid Res. 2001;42:390–8.

    Google Scholar 

  • Hanyu O, Nakae H, Miida T, Higashi Y, Fuda H, Endo M, Kohjitani A, Sone H, Strott CA. Cholesterol sulfate induces expression of the skin barrier protein filaggrin in normal human epidermal keratinocytes through induction of RORα. Biochem Biophys Res Commun. 2012;428(1):99–104.

    Google Scholar 

  • Haratake A, Ikenaga K, Katoh N, Uchiwa H, Hirano S, Yasuno H. Topical mevalonic acid stimulates de novo cholesterol synthesis and epidermal permeability barrier homeostasis in aged mice. J Invest Dermatol. 2000;114:247–52.

    Google Scholar 

  • Harris IR, Farrel AM, Grunfeld C, Holleran WM, Elias PM, Feingold KR. Permeability barrier disruption coordinately regulates mRNA levels for key enzymes of cholesterol, fatty acids and ceramide synthesis in the epidermis. J Invest Dermatol. 1997;109:783–7.

    Google Scholar 

  • Higashi Y, Fuda H, Yanai H, et al. Expression of cholesterol sulfotransferase (SULT2B1b) in human skin and primary cultures of human epidermal keratinocytes. J Invest Dermatol. 2004;122:1207–13.

    Google Scholar 

  • Hoppe T, Winge MC, Bradly M, Nordenskjold M, Vahlquist A, et al. X-linked recessive ichthyosis: an impaired barrier function evokes limited gene responses before and after moisturizing treatments. Br. J. Dermatol. 2012;167:514–522.

    Google Scholar 

  • Hydzik P, Szpak D. Side effects of the HMG-CoA reductase inhibitors (statins). Lupus erythematosus induced by atorvastatin therapy. Przegl Lek. 2011;68:495–8.

    Google Scholar 

  • Ikuta T, Chida K, Tajima O, et al. Cholesterol sulfate, a novel activator for the eta isoform of protein kinase C. Cell Growth Differ. 1994;5:943–7.

    Google Scholar 

  • Inoue M, Ooe M, Fuji K, Matsunaka M, Ichihashi M. Mechanisms of inhibitory effects of Co Q(10) on UVB-induced wrinkle formation in vitro and in vivo. Biofactors. 2008;32:237–43.

    Google Scholar 

  • Jackson SM, Wood LC, Lauer S, Taylor JM, Cooper AD, Elias PM, Feingold KR. Effect of cutaneous permeability barrier disruption on HMG-CoA reductase, LDL receptor, and apolipoprotein E mRNA levels in the epidermis of hairless mice. J Lipid Res. 1992;33:1307–14.

    Google Scholar 

  • Jetten AM, George MA, Pettit GR, et al. Action of phorbol esters, bryostatins, and retinoic acid on cholesterol sulfate synthesis: relation to the multistep process of differentiation in human epidermal keratinocytes. J Invest Dermatol. 1989;93:108–15.

    Google Scholar 

  • Jiang YJ, Lu B, Tarling E, Kim P, Man M-Q, Crumrine D, Edwards P, Elias PM, Feingold KR. Regulation of ABCG1 expression in human keratincoytes and murine epidermis. J Lipid Res. 2010;51:3185–95.

    Google Scholar 

  • Kang HS, Angers M, Beak JY, Wu X, Gimble JM, Wada T, Xie W, Collins JB, Grissom SF, Jetten AM. Gene expression profiling reveals a regulatory role for RORα and RORγ in phase I and phase II metabolism. Physiol Genomics. 2007;31:281–94.

    Google Scholar 

  • Kashiwagi M, Ohba M, Chida K, et al. Protein kinase C eta (PKC eta): its involvement in keratinocyte differentiation. J Biochem (Tokyo). 2002;132:853–7.

    Google Scholar 

  • Kielar D, Kaminski WE, Liebisch G, Piehler A, Wenzel JJ, Mohle C, Heilerl S, Langman T, Friedrich SO, Bottcher A, Barlage S, Drobnik W, Schmitz G. Adenosine triphosphate binding cassette (ABC) transporters are expressed and regulated during terminal keratinocyte differentiation: a potential role for ABCA7 in epidermal lipid reorganization. J Invest Dermatol. 2003;121:465–74.

    Google Scholar 

  • Kim S, Hee-Oh J, Lee Y, Le J, Cho KH, Chung JHO. Induction of tissue inhibitor of matrix metalloprotease-2 by cholesterol depletion leads to the conversion of pro MMP-2 into active MMP-2 in human dermal fibriblasts. Exp Mol Med. 2010;42:38–46.

    Google Scholar 

  • Kiortsis DN, et al. Statin-associated adverse effects beyond muscle and liver toxicity. Atherosclerosis. 2007;195:7–16.

    Google Scholar 

  • Komuves LG, Hanley K, Jiang Y, et al. Induction of selected lipid metabolic enzymes and differentiation-linked structural proteins by air exposure in fetal rat skin explants. J Invest Dermatol. 1999;112:303–9.

    Google Scholar 

  • Konig J, Nies AT, Cui Y, Leier I, Keppler D. Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance. Biochim Biophys Acta Biomembr. 1999;1461:377–94.

    Google Scholar 

  • Kuroki T, Ikuta T, Kashiwagi M, et al. Cholesterol sulfate, an activator of protein kinase C mediating squamous cell differentiation: a review. Mutat Res. 2000;462:189–95.

    Google Scholar 

  • Lavrijsen APM, Oestmens E, Hermans J, Bodde HE, Vermeer BJ, Ponec M. Barrier function parameters in various keratinization disorders: transepidermal water loss and vascular response to hexyl nicotinate. Br. J. Dermatol. 1993;129:547–554.

    Google Scholar 

  • Long SA, Wertz PW, Strauss JS, et al. Human stratum corneum polar lipids and desquamation. Arch Dermatol Res. 1985;277:284–7.

    Google Scholar 

  • Mabuchi H, Higashikata T, Kawashiri M, Katsuda S, Mizuno M, Nohara A, Inazu A, Koizumi J, Kobayashi J. Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients. J Atheroscler Thromb. 2005;12:111–9.

    Google Scholar 

  • Maloney ME, Williams ML, Epstein EH Jr, Law MY, Fritsch PO, Elias PM. Lipids in the pathogenesis of ichthyosis: topical cholesterol sulfate-induced scaling in hairless mice. J Invest Dermatol. 1984;83:252–6.

    Google Scholar 

  • Matsuda T, Shimada M, Sato A, Akase T, Yoshinari K, Nagata K, Yamazoe Y. Tumor necrosis Factor-alpha-Nuclear Factor-Kappa B signaling enhances St2b2 expression during 12-O-tetradecanoylphorbol-13-acetate-induced epidermal hyperplasia. Biol. Pharm. Bull. 2011;34:183–190.

    Google Scholar 

  • Menon GK, Feingold KR, Moser AH, Brown BE, Elias PM. De novo sterologenesis in the skin II. Regulation by cutaneous barrier requirements. J Lipid Res. 1985;26:418–27.

    Google Scholar 

  • Mirza R, Hayasaka S, Takagishi Y, Kambe F, Ohmori S, Maki M, Yamamoto K, Murakami T, Kaji D, Zadworny D, Murata Y, Seo H. DHCR24 gene knockout mice demonstrate lethal dermopathy with differentiation and maturation defects in the epidermis. J Invest Dermatol. 2006;126:638–47.

    Google Scholar 

  • Ohman H, Vahlquist A. The pH gradient over the stratum corneum differs in X-linked recessive and autosomal dominant Ichthyosis: a clue to the molecular origin of the “acid skin mantle”? J Invest dermatol. 1998;111:674–7.

    Google Scholar 

  • Ponec M, Williams ML. Cholesterol sulfate uptake and outflux in cultured human keratinocytes. Arch Dermatol Res. 1986;279:32–6.

    Google Scholar 

  • Proksch E, Elias PM, Feingold KR. Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements. J Clin Invest. 1990;85:874–82.

    Google Scholar 

  • Proksch E, Feingold KR, Elias PM. Epidermal HMG CoA reductase activity in essential fatty acid deficiency: barrier requirements rather than eicosanoid generation regulate cholesterol synthesis. J Invest Dermatol. 1992;99:216–20.

    Google Scholar 

  • Proksch E, Elias PM, Feingold KR. Localization and regulation of epidermal 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity by barrier requirement. J Clin Invest. 1995;95:2281–90.

    Google Scholar 

  • Quan T, Qui Z, Xia W, Shao Y, Voorhees JV, Fisher GJ. Matrix degrading metalloproteinases in photoaging. J Invest Dermatol Symp Proc. 2009;14:20–4.

    Google Scholar 

  • Ranasinghe AW, Wertz PW, Downing DT, Mackenzie IC. Lipid composition of cohesive and desquamated corneocytes from mouse ear skin. J Invest Dermatol. 1986;86:187–90.

    Google Scholar 

  • Rearick JI, Albro PW, Jetten AM. Increase in cholesterol sulfotransferase activity during in vitro squamous differentiation of rabbit tracheal epithelial cells and its inhibition by retinoic acid. J Biol Chem. 1987a;262:13069–74.

    Google Scholar 

  • Reed T, Ghadially R, Elias PM. Skin type, but neither race or gender, influence epidermal permeability function. Arch Dermatol. 1995;131:1134–8.

    Google Scholar 

  • Reed MJ, Purohit A, Woo LW, et al. Steroid sulfatase: molecular biology, regulation, and inhibition. Endocr Rev. 2005;26:171–202.

    Google Scholar 

  • Sato J, Denda M, Nakanishi J, Nomura J, Koyama J. Cholesterol sulfate inhibits proteases that are involved in desquamation of stratum corneum. J Invest Dermatol. 1998;111:1523–747.

    Google Scholar 

  • Schallreuter KU, Hasse S, Rokos H, Chavan B, Shalbaf M, Spencer JD, Wood JM. Cholesterol regulates melanogenesis in human epidermal melanocytes and melanoma cells. Exp Dermatol. 2009;18:680–8.

    Google Scholar 

  • Shimada M, Matsuda T, Sato A, Akase T, Matsubara T, Nagata K, Yamazoe Y. Expression of a skin cholesterol sulfotransferase, St2b2, is a trigger of epidermal cell differentiation. Xenobiotica. 2008;38:1487–1499.

    Google Scholar 

  • Shindo Y, Wit E, Han E, Epstein W, Packer L. Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J Invest Dermatol. 1994;102:122–4.

    Google Scholar 

  • Strott CA, Higashi Y. Cholesterol sulfate in human physiology: what’s it all about? J Lipid Res. 2003;44:1268–78.

    Google Scholar 

  • Tarling EJ, Edwards PA. ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter. PNAS. 2011;108:19719–24.

    Google Scholar 

  • Tyagi SC, Kumar S, Katwa L. Differential regulation of extracellular matrix metalloproteinase and tissue inhibitor by heparin and cholesterol in fibroblast cells. J Mol Cell Cardiol. 1997;29:391–404.

    Google Scholar 

  • Wertz PW, Downing DT. Integral lipids of human hair. Lipids. 1988;23:878–81.

    Google Scholar 

  • Williams ML, Elias PM. Stratum corneum lipids in disorders of cornification: increased cholesterol sulfate content of stratum corneum in recessive X-linked ichthyosis. J Clin Invest. 1981;68(6):1404–10.

    Google Scholar 

  • Zetterstein E, Man M-Q, Sato J, Denda M, Farrell A, Ghadially R, Williams ML, Feingold KR, Elias PM. Recessive x-Linked Ichthyosis: role of cholesterol-sulfate accumulation in the barrier abnormality. J Invest Dermatol. 1998;111:784–90.

    Google Scholar 

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Authors and Affiliations

  1. ASI Corporation, 1005 Route 202/206, 08807, Bridgewater, NJ, USA

    G. K. Menon

  2. UCSF, San Francisco, USA

    K. R. Feingold

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  1. G. K. Menon
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Correspondence to G. K. Menon .

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  1. Johnson & Johnson, Skillman, New Jersey, USA

    Apostolos Pappas

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Menon, G., Feingold, K. (2015). Chapter 6 Cholesterol Metabolism in the Epidermis. In: Pappas, A. (eds) Lipids and Skin Health. Springer, Cham. https://doi.org/10.1007/978-3-319-09943-9_6

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