Role of cholesterol sulfate in epidermal structure and function: Lessons from X-linked ichthyosis

Elias, Peter M.; Williams, Mary L.; Choi, Eung Ho; Feingold, Kenneth R.

doi:10.1016/j.bbalip.2013.11.009

Cited by 97 publications

(92 citation statements)

References 105 publications

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“…The cholesterol sulfate cycle among layers of the epidermis shifts CS content between 1 and 5% of lipids there and potently regulates differentiation, barrier function, cohesion, and scaling (Elias et al, 2014). CS is a marker of precancerous and cancerous lesions of the cervix and prostate (Cooks et al, 2011; Eberlin et al, 2010; Kiguchi et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Charge-Triggered Membrane Insertion of Matrix Metalloproteinase-7, Supporter of Innate Immunity and Tumors

et al. 2015

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SUMMARY Matrix metalloproteinase-7 (MMP-7) sheds signaling proteins from cell surfaces to activate bacterial killing, wound healing, and tumorigenesis. The mechanism targeting soluble MMP-7 to membranes has been investigated. NMR structures of the zymogen, free and bound to membrane mimics without and with anionic lipid, reveal peripheral binding to bilayers through paramagnetic relaxation enhancements. Addition of cholesterol sulfate partially embeds the protease in the bilayer, restricts its diffusion, and tips the active site away from the bilayer. Its insertion of hydrophobic residues organizes the lipids, pushing the head groups and sterol sulfate outward towards the enzyme's positive charge on the periphery of the enlarged interface. Fluorescence probing demonstrates a similar mode of binding to plasma membranes and internalized vesicles of colon cancer cells. Binding of bilayered micelles induces allosteric activation and conformational change in the auto-inhibitory peptide and the adjacent scissile site, illustrating a potential intermediate in the activation of the zymogen.

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Section: Introductionmentioning

confidence: 99%

Charge-Triggered Membrane Insertion of Matrix Metalloproteinase-7, Supporter of Innate Immunity and Tumors

et al. 2015

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“…However, the skin puts up a barrier function against the permeation of foreign materials into the viable epidermis (Curdy et al, 2001). This protective measure is to prevent water loss as well as to inhibit the invasion of pathogenic substances that will cause infection to the body (Elias et al, 2014; Feingold and Elias, 2014; van Smeden et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers

Boakye

Patel

Singh

2015

International Journal of Pharmaceutics

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The objectives of this study were to develop an innovative investigative model using doxorubicin as a fluorophore to evaluate the skin permeation of nanocarriers and the impact of size and surface characteristics on their permeability. Different doxorubicin-loaded liposomes with mean particle size <130nm and different surface chemistry were prepared by ammonium acetate gradient method using DPPC, DOPE, Cholesterol, DSPE-PEG 2000 and 1,1-Di-((Z)-octadec-9-en-1-yl)pyrrolidin-1-ium chloride (CY5)/DOTAP/1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) as the charge modifier. There was minimal release of doxorubicin from the liposomes up to 8 h; indicating that fluorescence observed within the skin layers was due to the intact liposomes. Liposomes with particle sizes >600nm were restricted within the stratum corneum. DOTAP (p<0.01) and CY5 (p<0.05) liposomes demonstrated significant permeation into the skin than DOPA and PEG liposomes. Tape stripping significantly (p<0.01) enhanced the skin permeation of doxorubicin liposomes but TAT-decorated doxorubicin liposomes permeated better (p<0.005). Blockage of the hair follicles resulted in significant reduction in the extent and intensity of fluorescence observed within the skin layers. Overall, doxorubicin liposomes proved to be an ideal fluorophore-based model. The hair follicles were the major route utilized by the liposomes to permeate skin. Surface charge and particle size played vital roles in the extent of permeation.

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“…Of note, the only compounds elevated in RXLI patients, independent of their age, are 5-cholesten-3 ␤ -ol-3-sulfate [cholesterol sulfate (CS)] and oxysterol sulfates ( 4 ). High levels of CS seem to be related to the skin scaling present in most of the RXLI males ( 5 ).…”

Section: Msmentioning

confidence: 99%

Simultaneous quantification of cholesterol sulfate, androgen sulfates, and progestagen sulfates in human serum by LC-MS/MS

Sánchez‐Guijo

Oji

Hartmann

et al. 2015

Journal of Lipid Research

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Human adrenal glands, and those of some primates, secrete high concentrations of conjugated steroids, particularly 5-androsten-3 ␤ -ol-17-one-3-sulfate [dehydroepiandrosterone sulfate (DHEAS)], which reaches different peripheral tissues through blood ( 1 ). Sulfonation increases the solubility of steroids in water-based biological fl uids such as blood or urine. Sulfated steroids, also known in the literature as steroid sulfates or steroid sulfonates, represent the most abundant fraction of steroids in human blood. Because the physiological activity has been traditionally assigned to the unconjugated steroids, the classical dogma assumes that sulfated steroids are inactive forms of steroids which require sulfate cleavage to be active . In this context, human steroid sulfatase (STS) is the enzyme that desulfates the sulfated steroids to obtain free forms. The complementary reaction, sulfonation, is provided by sulfotransferase enzymes ( Fig. 1 ). This cycle allows for the regulation and excretion of steroids.The concept of steroid sulfates as inactive compounds is under revision. A specifi c transporter for sulfated steroids in the human testis was recently described ( 2 ). Moreover, Abstract Steroids are primarily present in human fl uids in their sulfated forms. Profi ling of these compounds is important from both diagnostic and physiological points of view . Here, we present a novel method for the quantifi cation of 11 intact steroid sulfates in human serum by LC-MS/MS. The compounds analyzed in our method, some of which are quantifi ed for the fi rst time in blood, include cholesterol sulfate, pregnenolone sulfate, 17-hydroxy-pregnenolone sulfate, 16-␣ -hydroxy-dehydroepiandrosterone sulfate, dehydroepiandrosterone sulfate, androstenediol sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and dihydrotestosterone sulfate. The assay was conceived to quantify sulfated steroids in a broad range of concentrations, requiring only 300 l of serum. The method has been validated and its performance was studied at three quality controls, selected for each compound according to its physiological concentration. The assay showed good linearity (R 2 > 0.99) and recovery for all the compounds, with limits of quantifi cation ranging between 1 and 80 ng/ml. Averaged intra-day and between-day precisions (coeffi cient of variation) and accuracies (relative errors) were below 10%. The method has been successfully applied to study the sulfated steroidome in diseases such as steroid sulfatase deficiency, proving its diagnostic value. This is, to our best knowledge, the most comprehensive method available for the quantifi cation of sulfated steroids in human blood. -S á nchez-Guijo, A., V. Oji, M.

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Role of cholesterol sulfate in epidermal structure and function: Lessons from X-linked ichthyosis

Cited by 97 publications

References 105 publications

Charge-Triggered Membrane Insertion of Matrix Metalloproteinase-7, Supporter of Innate Immunity and Tumors

Charge-Triggered Membrane Insertion of Matrix Metalloproteinase-7, Supporter of Innate Immunity and Tumors

Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers

Simultaneous quantification of cholesterol sulfate, androgen sulfates, and progestagen sulfates in human serum by LC-MS/MS

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