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At least 19 recordsLinked to original sources
PubMed1982

Histidine-rich protein of the keratohyalin granules. Source of the free amino acids, urocanic acid and pyrrolidone carboxylic acid in the stratum corneum.

The pool of free amino acids, urocanic acid and pyrrolidone carboxylic acid in mammalian stratum corneum has been shown to be derived principally or totally from the histidine-rich protein of the keratohyalin granules. The time course of appearance of free amino acids and breakdown of the histidine-rich protein are similar, as are the analyses of the free amino acids and the histidine-rich protein. Quantitative studies show that between 70 and 100% of the total stratum corneum-free amino acids are derived from the histidine-rich protein.

Amino Acids↗
PubMed2002

Some photophysical studies of cis- and trans-urocanic acid.

Urocanic acid, an important human skin chromophore, undergoes a variety of photochemical transformations when exposed to the near-UV portion of sunlight and natural daylight, the principal reaction being the transformation from the stable trans- or (E)-form of the chromophore (trans-UA) to the biologically active cis- or (Z)-form (cis-UA), which is claimed to induce immunosuppression linked to the onset of skin cancer. This study is concerned with the comparative photophysical behaviour of the two urocanic acid isomers in aqueous solution using both continuous irradiation and pulsed irradiation techniques. The UV absorption maximum for both isomers occurs in the region of 270 nm with the absorption shape varying characteristically with pH, the cis-isomer showing a lower overall molar absorptivity. Both isomers exhibit weak fluorescence (quantum yields estimated to be less than 10(-4)) with each isomer showing small differences in the way in which pH and excitation wavelength influence the fluorescence emission characteristics. Pulsed nanosecond laser irradiation at 266 nm of aqueous solutions at pH 7 shows that both isomers undergo photo-ionisation with a quantum yield of 0.02 for the hydrated electron production, a quantum yield value comparable with that for photoisomerisation at this wavelength. Laser flash studies also show that the photo-ionised species reacts efficiently with oxygen (quenching rate kQ = 1.3 x 10(9) M(-1) s(-1)), while some preliminary experiments indicate that both cis- and trans-urocanic acids react with the semiquinone radical of L-3,4-dihydroxyphenylalanine (L-DOPA) with a fast reaction rate constant of approximately 5 x 10(7) M(-1) s(-1). The photophysical characteristics of trans-UA and cis-UA reported here are discussed in the context of other recent pulsed irradiation studies on urocanic acid over nanosecond and picosecond time scales, in an attempt to clarify the complex photo-behaviour of this interesting biomolecule.

Humans↗
PubMedDate not supplied

The effect of molecular environment on the photoisomerization of urocanic acid.

Urocanic acid, imidazole propenoic acid, is a metabolic product of histidine, which accumulates in skin and is excreted in sweat. It absorbs UV radiation at wavelengths shorter than 340 nm, and its principal photochemical reaction is a trans-cis isomerization about the propenyl double bond. This isomerization to the biologically active cis isomer is implicated in the photoinduced suppression of the immune system of skin. The kinetics of the trans --> cis photoisomerization of urocanic acid has been determined in a number of solvents, spanning a range of polarities. The initial rates of isomerization and the photostationary trans-cis compositions, in all solvents except water, correlate linearly with solvent polarity. This indicates that the isomerization proceeds through a polar intermediate that is stabilized by coulombic interactions with the molecular environment.

Isomerism↗
PubMed2002

Interference-based electrochemical biosensor for the measurement of the concentration and isomer ratio of urocanic acid.

Urocanic acid (UCA) is known to be synthesized as the trans isomer (trans-UCA) in the skin, and trans-UCA is transformed by UV light to the cis isomer (cis-UCA), which may be involved in photoimmunosuppression. An electrochemical method has been developed for the measurement of the concentration and isomer ratio of UCA. A heme peptide-modified electrode (HP electrode) reduces hydrogen peroxide at +150 mV vs Ag/AgCl, and the reduction current is inhibited by UCA. Since cis-UCA is a stronger inhibitor than trans-UCA, irradiation of a sample solution with UV light increases the percent inhibition. The concentration and isomer ratio of UCA in the sample solution can be estimated from the values of percent inhibition before and after the UV irradiation.

Biosensing Techniques↗
PubMed1996

Expression of CD80 (B7/BB-1) and CD28 in human white blood cells treated with urocanic acid.

Urocanic acid (UCA) is formed in the epidermis where it accumulates to be converted from trans- to cis-UCA by ultraviolet (UV) radiation. The two isomers modulate immune functions in several experimental systems. In particular, cis-UCA has been shown to induce antigen-specific immune tolerance, but the molecular mechanism of this effect is unknown. The present investigation was instituted to disclose any effect of UCA isomers on the cellular expression of the costimulatory antigens CD80 (B7/BB-1) and CD28. CD80 expression was efficiently induced in monocytic (CD14+) cells by human interferon-gamma, while CD28 levels on lymphocytes remained unchanged, as detected by flow cytometry. Neither UCA isomer showed any effect on the expression patterns of these costimulatory molecules. The results obtained suggest that the mode of action for epidermal UCA-induced tolerogenesis may not involve modulation of CD80 (B7/BB-1) or CD28 expression.

Antigen Presentation↗
PubMed1996

The sunscreening effect of urocanic acid.

Urocanic acid (UCA), present in the stratum corneum, is a major absorber of ultraviolet (UV) radiation and, on UV exposure, is induced to isomerize from the naturally occurring trans-isomer to the cis-isomer. Cis-UCA has been shown to have immunosuppressive properties, while trans-UCA may act as a natural sunscreen due to its UV-absorbing properties. The photoprotective capacity of UCA was investigated in this study. Minimal erythema dose (MED) was determined on normal buttock skin in 36 healthy subjects and the concentration of UCA isomers was measured on the skin adjacent to the test site. On the contralateral buttock. MED was determined 20 min after application of trans-UCA 5% in a cream base. The UCA cream gave a sun protection factor of 1.58. The amount of UCA applied was, however, 20-200 times higher than the amount of UCA found in normal skin, making a sunscreening effect of naturally occurring UCA very low. This was further supported, by a lack of correlation between naturally occurring UCA and the UV sensitivity of each subject determined by the MED.

Adolescent↗
PubMed1990

The effect of histamine receptor antagonists on immunosuppression induced by the cis-isomer of urocanic acid.

Urocanic acid (UCA) is found in the stratum corneum predominantly as the trans-isomer; on ultraviolet B (UVB) irradiation, isomerization to the cis-isomer occurs. Cis-UCA has been shown to mimic the consequences of UVB irradiation in generating transient suppression of contact and delayed hypersensitivity (DH) responses. In an attempt to elucidate the mechanisms of action of UCA, the effects of 2 histamine receptor antagonists, cimetidine and terfenadine, were examined. One day after skin painting murine ears with cis-UCA, the number of ATPase- cells was reduced from 1068 to 408 mm-2. However, if cimetidine or terfenadine was applied at the same time as cis-UCA, the number of ATPase- cells was reduced only slightly from the control value, to 1028 and 892 respectively. Cis-UCA given subcutaneously or epidermally 5 h before infection of mice with herpes simplex virus suppressed the DH response on subsequent challenge with the virus. If cimetidine or terfenadine was added at the same time as cis-UCA, little suppression of the DH response to the virus occurred. Thus 2 effects of cis-UCA, on the number of ATPase+ epidermal cells and on DH response, were reduced or abrogated by histamine receptor antagonists, which may indicate that cis-UCA acts through histamine-like receptors in the skin.

Adenosine Triphosphatases↗
PubMed2002

Photogeneration and quenching of reactive oxygen species by urocanic acid.

Urocanic acid, UCA, is characterized by two electronic transitions in the UV-B (280-320 nm) which comprise its broad absorption spectrum and give rise to wavelength-dependent isomerization quantum yields. The absorption spectrum of UCA extends into the UV-A (320-400 nm). Given the UV-A component of sunlight is significantly greater than the UV-B component it is hypothesized even weak UV-A photochemistry of UCA could be important for in vivo responses to UV radiation. Degenerate pump-probe experiments performed on t-UCA at several wavelengths in the UV-A reveal an excited-state absorption that undergoes a rapid, approximately 1 ps decay. Photoacoustic experiments performed on both the cis and trans isomers reveal the formation of a long-lived intermediate following UV-A excitation. The efficiency and action spectra for this latter photoactive process are presented and are similar for both isomers of UCA. Cholesterol hydroperoxide assays designed to investigate the nature of the UV-A photoreactivity of t-UCA confirm the production of reactive oxygen species. The bimolecular rate constant for the quenching of singlet oxygen by t-UCA is determined to be 3.5 x 10(6) M(-1) s(-1). Taking into consideration recent theoretical calculations and jet expansion studies of the electronic structure of gas-phase t-UCA, a model is proposed to explain the isomerization and photoreactivity of t-UCA in solution over the UV-A region.

Cholesterol↗
PubMed1998

Regulation of stimulated cyclic AMP synthesis by urocanic acid.

Urocanic acid (UCA) has been shown to mediate the UVB radiation-induced immunosuppression initiated in the skin by UV-induced isomerization from the trans to the cis isomer. However, the mechanism by which cis-UCA acts is still unclear. Therefore, the present study was undertaken to determine the effect of trans- and cis-UCA on cyclic adenosine 3',5'-monophosphate (cAMP) synthesis in human dermal fibroblasts, Golden Syrian hamster hepatocytes and in the human adenocarcinoma cell line, HT29. Neither trans- nor cis-UCA was able to stimulate cAMP synthesis directly in any of the models tested. In human dermal fibroblasts, cis-UCA, in contrast to trans-UCA, specifically inhibited cAMP synthesis induced by either prostaglandin (PG) E1 or PGE2 with a maximum inhibitory effect of 25-30% at cis-UCA concentrations greater than 1 microM and half-maximum inhibitory effect (EC50) observed at 35 nM. The effect of cis-UCA was not to stimulate phosphodiesterase and cAMP breakdown. The inhibitory effect of cis-UCA (an imidazole derivative) was not mediated through stimulation of the alpha 2-adrenergic receptor. The inhibitory effect of cis-UCA on stimulated cAMP synthesis was a function of the cell density and was only significant when the fibroblasts were confluent or postconfluent. In contrast to the studies with human dermal fibroblasts, an inhibitory effect of cis-UCA was not observed in either isolated hamster hepatocytes or HT29 cells, in which cAMP synthesis was stimulated by glucagon and vasoactive intestinal peptide, respectively. These results point to a possible regulation of cAMP synthesis in fibroblasts as one mechanism by which cis-UCA exerts its biological effect in the skin.

Adrenergic alpha-Agonists↗
PubMed1997

Regulation of tumor antigen presentation by urocanic acid.

Urocanic acid (UCA) accumulates in the epidermis after deamination of histidine. UCA isomerizes from the trans to the cis form upon exposure to environmental UV radiation. Cis-UCA is immunosuppressive in several models. Topically applied cis-UCA was reported to enhance the cutaneous tumor yield in chronically UV-irradiated mice, suggesting involvement of cis-UCA in photocarcinogenesis. Since Langerhans cells (LC) are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor-immune responses, we examined the effects of trans- and cis-UCA on LC tumor Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2a). In this system, induction of immunity requires exposure of LC to granulocyte-macrophage CSF. Naive CAF1 (H-2(a/d)) mice were immunized against S1509a by injection with granulocyte-macrophage CSF-exposed and TAA-pulsed epidermal cells (EC), as assessed by growth inhibition of inoculated tumor cells. Incubation of EC in cis-, but not trans-UCA completely inhibited Ag presentation in this system. Neither histamine antagonists nor indomethacin reversed these effects of cis-UCA. The ability of trans- and cis-UCA to modulate EC presentation of TAA for secondary immune responses was also examined. EC were pulsed with TAA in vitro and then injected into hind footpads of tumor-immune mice. After 24 h, footpad swelling was assessed as a measure of delayed-type hypersensitivity. Incubation with cis-, but again not trans-UCA before TAA exposure significantly inhibited elicitation of delayed-type hypersensitivity. These data indicate that cis-UCA may be an important regulator of LC Ag-presenting function in tumor-immune responses, and thus may play a role in photocarcinogenesis.

Animals↗
PubMed1993

Characterization of a monoclonal antibody to cis-urocanic acid: detection of cis-urocanic acid in the serum of irradiated mice by immunoassay.

Cis-urocanic acid (cis-UCA), which is formed from the naturally occurring trans-isomer on ultraviolet (UV) irradiation, has been suggested as a photoreceptor for and mediator of the suppressive effects of UV irradiation on systemic immune responses. Trans-UCA is located predominantly in the stratum corneum, and the extent of isomerization to cis-UCA may be analysed by high-performance liquid chromatography (HPLC) of skin extracts. Such an analysis is not suitable for other tissues. In this study a murine monoclonal antibody to cis-UCA was prepared and tested by ELISA using UCA isomers conjugated to protein as antigens. The interaction of the antibody with structural analogues of UCA was assessed by competitive inhibition ELISA which indicated that the antibody had a high specificity for cis-UCA. Screening of sera at various times after UVB irradiation of mice by competitive inhibition ELISA using the monoclonal antibody showed that cis-UCA was present, probably in an unbound form, for at least 2 days after the exposure. Thus, cis-UCA produced in the epidermis following UVB irradiation reaches the serum a few hours later. The implications of this finding for the generation of suppressed immune responses are discussed.

Animals↗
PubMed1999

The degradation of L-histidine and trans- and cis-urocanic acid by bacteria from skin and the role of bacterial cis-urocanic acid isomerase.

UV-B radiation suppresses cell-mediated immunity. Histidine forms trans-urocanic acid (trans-UCA) enzymatically in the stratum corneum. Photoisomerization of trans-UCA to cis-urocanic acid (cis-UCA) has been proposed for the initiation of an immunosuppressive process. Many microorganisms described in the literature metabolize histidine and/or trans-UCA. Our enrichment cultures of soil and sewage contain organisms that can degrade cis-UCA. We have tested microorganisms for degradation of cis-UCA, trans-UCA, or L-histidine when they are incorporated at 0.2% in nutrient broth. Six out of 10 selected genera isolated by our clinical microbiology laboratory degrade one or more of the imidazole substrates. We have cultured over 60 aerobic isolates from human skin. Of these, 33 degrade one or more of the three imidazole substrates and 12 degrade cis-UCA. Isolates from BALB/c mice are also active on cis-UCA. We have identified a cis-UCA-degrading bacterium as Micrococcus luteus. Four ATCC strains of M. luteus have been tested and three are active on histidine or trans-UCA; two are active on cis-UCA. Micrococci that degrade cis-UCA contain a new enzyme, cis-UCA isomerase, which converts the substrate to the trans-isomer. This enzyme provides access to the classical L-histidine degradation pathway. We hypothesize that an epidermal microflora that degrades L-histidine, trans-UCA, or cis-UCA influences the concentration of urocanic acids on the skin and, thus, affects immune suppression.

Adult↗