Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysosomes are by definition organelles that maintain an internal acidic pH and contain hydrolytic enzymes. Membrane-coating granules contain a battery of hydrolytic enzymes, in addition to their lamellar discs, and are therefore commonly assumed to be lamellate lysosomes. Although there are data confirming the existence of enzymes in membrane-coating granules, there is no direct evidence to suggest that their internal pH is acidic. As part of a wider program on their role in desquamation, our aim was to determine whether membrane-coating granules are indeed acidic and possess proton pumps. Chloroquine and monensin were selected as the pH markers because both induce swelling of acidic organelles. In four repeat experiments dermatome slices of pig ear skin (2 mm2 x 0.5 mm) were incubated as organ cultures either alone (control) or with 1 mM chloroquine or 25 microM monensin. Ultrastructural observations revealed no swelling in control specimens. In contrast, the inclusion of chloroquine or monensin caused swelling of specific organelles including membrane-coating granules, lysosomes, and trans elements of Golgi stacks, but not mitochondria, rough endoplasmic reticulum, or nuclear envelopes. Swelling of membrane-coating granules and the other organelles was prevented by pretreatment with N,N'-dicyclohexylcarbodiimide, a known inhibitor of lysosomal H+ ATPase activity. These findings suggest that membrane-coating granules actively maintain an acidic interior with the aid of proton pumps. Furthermore, membrane-coating granules are heterogeneous because swelling of the whole population did not commence simultaneously. However, it remains to be determined whether this heterogeneity reflects variations in membrane-coating granule pH, leakiness of their membranes to cations, or the number or activity of their proton pumps.
J Invest Dermatol 1989 Oct
PMID:Membrane-coating granules are acidic organelles which possess proton pumps. 255 May 59

To study some of the biochemical and physical states of membranes associated with hyperproliferation, the effect of topical hexadecane on membrane fluidity in guinea pig epidermis was investigated by electron spin resonance using a 5-doxylstearic acid spin labeling agent. Guinea pig epidermal cells were separated into three regions of keratinocytes by Percoll density gradient centrifugation. Membrane fluidity and Na+, K+-ATPase activity were higher in hyperproliferating epidermal cells than in control. The free cholesterol content and the molar ratio of free cholesterol to phospholipid were found to decrease significantly. Also elevated levels of palmitic acid, stearic acid and omega-3 unsaturated fatty acid derived from phospholipid were observed. Normal differentiation of epidermis was found to be accompanied by a decrease in membrane fluidity, whereas a relatively high membrane fluidity was maintained in the hexadecane-induced hyperproliferation.
J Invest Dermatol 1989 Nov
PMID:Changes of electron spin resonance membrane fluidity in hexadecane-induced hyperproliferative epidermis. 255 72

Monofunctional psoralens produce less phototoxicity than bifunctional psoralens after ultraviolet A (UVA) irradiation. We investigated the effect of repetitive treatments with angelicin (isopsoralen), a monofunctional psoralen, plus UVA radiation (IPUVA) on the number and morphology of dendritic epidermal cells (dEC). This effect was compared with that of 8-methoxypsoralen plus UVA radiation (PUVA), UVA alone, and UVB radiation. C3H/HeN mice were treated topically with the drugs three times/wk for 4 consecutive wk; followed each time by 1 or 2.5 J/cm2 of UVA radiation. Other groups of mice were treated with the drugs alone, UVA alone, or 0.81 J/cm2 of UVB. Epidermal sheets were stained for ATPase, Ia, and Thy-1 markers. Mice treated with PUVA and UVB exhibited severe phototoxicity, whereas no overt phototoxicity was observed in mice treated with IPUVA, UVA alone, or the drugs alone. Early during the PUVA and UVA treatments the ATPase marker was lost from dEC, followed by loss of the Ia marker; the Ia marker was lost before the ATPase marker from dEC in animals treated with IPUVA. At the end of the treatment, however, nearly total depletion of ATPase+, Ia+, and Thy-1+ dEC was observed in mice treated with PUVA and IPUVA. UVB radiation caused rapid depletion of Thy-1+ dEC as well as ATPase+ and Ia+ cells. During treatments with IPUVA, PUVA, UVA, and UVB, the Langerhans cells became rounded and lost their dendrites. These changes were quantitated by image analysis. We conclude that alterations of cutaneous immune cells can occur in the absence of overt phototoxicity, and that monofunctional and bifunctional psoralens plus low dose of UVA radiation may have different effects on dEC markers.
J Invest Dermatol 1989 May
PMID:Effect of psoralens and ultraviolet radiation on murine dendritic epidermal cells. 256 31

The role of Langerhans cells (LC) in host resistance against the induction and growth of nonmelanoma skin cancers is still obscure. The purpose of this study was to investigate the sensitivity of LC to simulated solar radiation in patients with basal cell carcinoma (BCC). Thirty-four patients (31-74 years old) with at least one histologically diagnosed BCC on a sun-exposed area and 21 healthy volunteers (29-62 years old) were included in the study. Patients and control subjects were given 10 graded doses of simulated solar UV radiation (10-75 mJ/cm2) on the lower back using a 12S solar simulator with a WG 320 filter. Twenty-four hours later, the minimal erythema dose (MED) was determined and shave biopsies were taken from the site given 1.25 X MED and from adjacent, unirradiated skin. Epidermal sheets were stained for LC using the ATPase method. The mean value of the MED of the BCC patients was 25 +/- 2 mJ/cm2 and that of controls was 29 +/- 3 mJ/cm2 (p greater than 0.05). The number of ATPase+ LC was significantly decreased (p less than 0.05), and their morphology was altered in the irradiated skin of nearly all individuals. However, there was no significant difference in the average reduction of LC in the patients (32% +/- 3%) compared with that of control subjects (32% +/- 4%). The depletion of LC ranged from 0% to 74% in different individuals, all of whom were given 1.25 MED. Furthermore, no correlation was found between the percentage decrease in ATPase+ cells and the dose of UV radiation required to produce erythema. Our results indicate that the ability of UV radiation to cause erythema was unrelated to the magnitude of its effects on LC number or morphology. Second, the morphologic alterations of LC in BCC patients after UV irradiation do not differ from those observed in normal individuals. Third, as a group, patients with BCC do not have a significantly lower MED than cancer-free subjects.
J Invest Dermatol 1989 Dec
PMID:The sensitivity of Langerhans cells to simulated solar radiation in basal cell carcinoma patients. 258 39

Epidermal Langerhans cells (LCs) are bone marrow-derived immune cells in the epidermis. Recently, we reported that adenosine triphosphatase (ATPase)-positive LC density in the hind-limb skin of male mice was lower than that of female and that orchiectomy resulted in an increase in LC density, though ovariectomy had no significant effect. To further investigate the control mechanisms of sex differences in LC density, the effect of systemic and topical application of testosterone propionate (TP) on LC density was examined in C57BL/6 mice. Subcutaneous injections of TP 5.8 X 10(-8) mol (20 micrograms)/day/mouse for 14 d resulted in a significant decrease in LC density both in orchiectomized males and normal females, and such an effect was also observed in adrenalectomized mice, suggesting that this effect of TP is not indirectly mediated by glucocorticosteroids. TP was also effective when applied as an ointment (1% or 5%) to the right hind-limb skin of both orchiectomized males and normal females for 14 d; namely, the LC density of the right hind-limb was lower than that of the left. Beta-estradiol and progesterone 5.8 X 10(-8) mol/day/mouse had no significant effect on LC density when systemically applied for 14 d to normal males and females. These results suggest that sex differences in LC density may result from higher concentrations of testosterone or its metabolites in males, and that the function of testosterone may be local.
J Invest Dermatol 1989 Jan
PMID:Effect of systemic and topical application of testosterone propionate on the density of epidermal Langerhans cells in the mouse. 264 15

This study reviews data on the histogenesis of Kaposi's sarcoma and angiosarcoma derived from clinical features, histology, electron microscopy, enzyme histochemistry, and immunochemistry of both diseases. Their hemorrhagic clinical appearance contrasts the predominantly lymphatic histologic features of vessels in early lesions. Investigations performed to resolve the debate whether these tumors arise from blood vessel or lymphatic endothelium show remarkably similar results for both conditions. Electron microscopy reveals Weibel - Palade bodies in a minority of cases, but features consistent with less well-differentiated blood vessel endothelium may be seen in a greater proportion of tumors. Enzyme histochemistry generally shows absence of adenosine triphosphatase and alkaline phosphatase in tumor cells; a pattern of enzymes similar to that found in normal lymphatic endothelium. Conflicting data arises from the large number of immunohistochemical studies performed on both conditions. Factor VIII-related antigen and Ulex europaeus agglutinin-I have been most frequently employed, but the specificity of these agents for blood vessel endothelium is debatable. Panendothelial markers show consistent labeling of both tumors, but marker studies employing a wide range of monoclonal antibodies specific for blood vessel endothelium have shown occasional positive labeling of tumor cells. A number of studies have claimed absence of labeling with specific blood vessel monoclonal antibodies, but at present no study employing a specific marker for lymphatic endothelium has been reported. Although the demonstration of specific markers for blood vessel endothelium in these tumors has been variable, the data would be compatible with lesions arising from undifferentiated stem cells that proliferate with varying degrees of differentiation toward blood vessel endothelium. An alternative hypothesis for the histogenesis of Kaposi's sarcoma would be one of multicentric hyperplasia containing lymphatic venular anastamoses with elements of both lymphatic and blood vessel endothelium.
J Invest Dermatol 1989 Aug
PMID:Histogenesis of Kaposi's sarcoma and angiosarcoma of the face and the scalp. 266 17

The effects of local hyperthermia treatment on contact sensitivity (CS) and on the number of Langerhans cells (LCs) were studied in mice. CS was significantly suppressed when mice were sensitized in the hyperthermia treated skin I, 2 or 4 days after treatment (43 degrees C for 45 min). This suppressive effect was not observed 7 or 14 days after the treatment. CS was also suppressed when mice were sensitized in non-treated skin I day after the treatment. The density of LCs detected as ATPase-positive cells also decreased significantly 1, 2, 4 and 7 days after the treatment. There appeared to be a positive correlation between the number of LCs and the extent of CS when mice were sensitized at hyperthermia treated skin. It was observed that this suppressive effect on CS was dose- and temperature-dependent. It could be transferred by spleen cells from the hyperthermia treated and DNFB-sensitized donors, and was antigen specific when spleen cells were transferred before sensitization of the recipient mice. This indicated it was, in part, associated with the induction of suppressor cells. These findings suggest that local hyperthermia treatment reduces the number of LCs with subsequent suppression of the induction phase of delayed-type hypersensitivity by the generation of antigen-specific suppressor cells.
Br J Dermatol 1989 Apr
PMID:Suppression of contact sensitivity by local hyperthermia treatment due to reduced Langerhans cell population in mice. 273 Aug 41

We investigated the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas located on the sun-exposed skin of 10 patients. Using adenosine triphosphatase-stained epidermis from the tumors, we compared the Langerhans' cells in squamous cell carcinoma with those in nontumorous skin specimens from the same patient. The nontumorous skin specimen was obtained from either sun-exposed perilesional or non-sun-exposed sites. In three patients a normal number and almost normal morphology of Langerhans' cells were observed within the epidermal component of the tumor. One patient showed a normal number but a profound alteration of the morphology of the cells. In the remaining six patients, a significant decrease in the number of Langerhans' cells was observed. Langerhans' cells within the epidermal component of the tumors of these patients exhibited morphologic alterations in that they were mainly round or oval rather than highly dendritic. In none of our patients was the number of Langerhans' cells in the tumor increased. We conclude that a decreased number and altered morphology of Langerhans' cells occur in some, but not all, squamous cell carcinomas of the skin, and that there is no apparent difference between the number of Langerhans' cells in sun-exposed vs unexposed skin from the same individual.
Arch Dermatol 1989 Jul
PMID:Variations in the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas. 249 13

Human skin was irradiated in vivo with a single UVB dose (100 mJ/cm2 or 200 mJ/cm2) to examine simultaneously the antigen-presenting function and interleukin-1 (IL-1) production capacity of irradiated epidermal cells (EC). Suction blisters were produced on irradiated areas on days 0, 3 and 7 after UVB. Irradiated EC were harvested and co-cultured with autologous T lymphocytes in the presence of antigens (PPD, HSV) or mitogen (ConA). Culture supernatants were tested for IL-1 activity using the thymocyte comitogenity assay. We found that a single 200 mJ/cm2 dose of UVB caused an immediate suppression of the antigen-presenting function of EC, but no alteration in their IL-1 production capacity or surface marker expression (ATPase, CDI). PPD- and HSV-induced lymphocyte proliferation was decreased 70-80% and ConA-driven proliferation 30% when compared to non-irradiated EC. However, this suppression was restored on days 3 and 7 after UVB irradiation, this being coexistent with an increased capacity of EC to produce IL-1. It remains to be elucidated whether the immediate UVB-induced photoimmunosuppression observed in the present study is due to inhibitory mediators or impaired membrane function of EC or both.
Br J Dermatol 1989 May
PMID:Immediate decrease in antigen-presenting function and delayed enhancement of interleukin-1 production in human epidermal cells after in vivo UVB irradiation. 278 7

The dynamic properties of plasma membrane in epidermal cells were determined by means of electron spin resonance using two kinds of doxyl stearic acid spin labeling agents: 5-DSA and 12-DSA. 5-DSA and 12-DSA are stearic acid analogues with a nitroxide radical ring at the 5th and 12th carbon positions, and these motions reflect molecular motion of lipid bilayer surrounding the hydrophilic region and the hydrophobic region, respectively. Guinea pig epidermal cells were separated into three regions of keratinocytes by Percoll density gradient centrifugation; the upper, middle, and lower epidermal cells. The order parameter S values for 5-DSA and 12-DSA incorporated into the isolated keratinocytes increased, suggesting a decrease in the plasma membrane fluidity, as cells approached the upper epidermal cell layer. The Na+,K+-ATPase activity as a plasma membrane-bound enzyme was determined in each epidermal cell region, and was found to decrease gradually as the cells approached the upper layer. Accordingly, the differentiation of epidermal cells in the keratinization process was found to be associated with a decrease in plasma membrane fluidity and with a decline of Na+,K+-ATPase activity.
Arch Dermatol Res 1988
PMID:Changes of membrane fluidity and Na+,K+-ATPase activity during cellular differentiation in the guinea pig epidermis. 283 81


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