Ornithine decarboxylase in skin.
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Biomedical subjects
Publications and source records attributed to L A Goldsmith.
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Ornithine decarboxylase (OCD; EC 4.1.1.17) activity is induced in dorsal rat skin by either application of the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) or by hair plucking. In TPA-treated rat skin, ODC activity does not rise above controls until 3 hr posttreatment. Following a peak at 4 hr, ODC activity declines until it reaches control levels at 12 hr. In contrast, stimulation of skin by hair plucking causes a 50% decrease in ODC activity by 1 hr. Enzyme activity then increases linearly to a peak at 4 hr and remains at 3 times control levels up to 12 hr. In skin stimulated by both hair plucking and TPA, and peak activity is found to exceed the maximum of either stimulus alone in an additive manner. The response to TPA occurs mainly in the epidermis, while both the epidermis and dermis show a substantial response to hair plucking. Both stimuli cause a lengthening of the half-life of ODC. Stimulation of ODC by hair plucking is insensitive to indomethacin administration but the TPA-response is inhibited 74%. Stimulation of ODC by hair plucking is inhibited by Actinomycin D only if Actinomycin D is given at the time of stimulus administration, and then only partially. The TPA-response is fully inhibited by Actinomycin D if given at the time of TPA application. Inhibition is roughly proportional to the duration of Actinomycin D treatment up to the activity peak at 4 hr. These results indicate that the tumor promoter, TPA, and the more physiological stimulus, hair plucking, stimulate skin ornithine decarboxylase activity by different mechanisms.
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A transglutaminase was extracted from cultured human prostatic adenocarcinoma cells. The enzyme did not exist as a zymogen and had an apparent molecular weight of 72,000 +/- 4,000 by gel filtration. Although the role of this transglutaminase in the human prostate is uncertain, it may be a useful marker for prostatic cells in vitro.
A new synthetic oral retinoid, 13-cis retinoic acid, is fairly well tolerated in patients and appears to be effective in those with Darier's disease and lamellar ichthyosis. It is less effective in those with pityriasis rubra pilaris. The mechanism of action of 13-cis retinoic acid in disorders of keratinization is unknown at the present time; however, it does not appear to cause lysosomal proliferation in therapeutic doses.
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The toxicity of parathion and its metabolite paraoxon was examined in the crayfish Orconectes rusticus and the snail Viviparus malleatus and attempts were made to relate this to parathion uptake and metabolism. The crayfish was found to be very susceptible with all animals tested dying at 0.1 ppb of parathion in 48 hours. The snail was resistant to exposure to 1000 ppm. The absence of lethality even to injected (50 mg/kg) parathion and paraoxon suggests an innate lack of susceptibility. Metabolism of the compounds could not be detected in vitro or in vivo in either species.
We have successfully used 5% sodium pyruvate in Eucerin for the treatment of congenital disorders with hyperkeratosis. It was most effective in those disorders with the most hyperkeratosis, and it was nonirritating even after extensive use. The efficacy of pyruvate may be due to the relatively low pKa of pyruvic acid.
A middle-aged adult male with a mild form of tyrosinemia II (Richner-Hanhart syndrome) is described. Treatment with a low-tyrosine diet caused a fall in plasma tyrosine and clearing of the hyperkeratosis of the soles. Liver biopsy of this patient revealed low but measurable levels of cytoplasmic tyrosine aminotransferase and elevated levels of the mitochondrial tyrosine-metabolizing enzyme aspartate aminotransferase. It is hypothesized that these enzymes have been induced in sufficient amounts to account for the mild clinical course.
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Potential in vivo substrates for epidermal transglutaminase have been isolated and partially characterized in human stratum corneum and new born rat epidermis. [14C]Putrescine and dansylcadaverine were incorporated into epidermal proteins in vitro. Two high molecular weight proteins incorporated the labels in both the rat ahd human homogenates. One of the proteins was too large to enter a 4% sodium dodecyl sulfate-polyacrylamide spacer gel; the other was seen at the interface between the spacer gel and a 10% sodium dodecyl sulphate-polyacrylamide running gel. These proteins were present in a buffer extract, sodium dodecyl sulphate-dithiothreitol extract and NaOH extract. The labels were also incorporated into protein in the insoluble pellet remaining after the afore-mentioned extractions. The incorporation of putrescine and dansylcadaverine was time dependent, and was inhibited by known inhibitors of epidermal transglutaminase. The two high molecular weight proteins had similar amino acid composition, characterized by high glycine, glutamic acid, serine and aspartic acid. The amino acid composition was similar to, although not identical with, the amino acid composition of alpha-keratin proteins. Epidermal homogenates incubated in the presence of transglutaminase showed progressive insolubilization of the protein. This cross-linking was inhibited by putrescine. [14C]Glycine, [14C]histidine and [4C]proline were incorporated into epidermal proteins in newborn rats in vivo. The glycine-labelled protein became progressively more insoluble when incubated in vitro in the presence of transglutaminase. In vitro incubation with transglutaminase had no effect on the histidine-and proline-labelled proteins.
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Ornithine decarboxylase (ODC; E.C.4.1.1.17) activities can be stimulated 2-10 fold in rat epidermis and dermis by hair plucking. Stimulation does not involve the removal of a soluble ODC inhibitor. ODC activity in the dermis and whole skin decreased with aging, while the epidermis showed little change. The apparent Km for ornithine and the heat stability of ODC in plucked and unplucked skin were similar. ODC was assayed in plucked and unplucked skin of rats fed diets containing between 2 and 24% protein. Activities in both plucked and unplucked skin were higher in the animals fed diets with higher protein contents. ODC levels were positively correlated with the weight changes undergone by rats on controlled-protein diets. In animals restricted to 2% protein diets and rehabilitated with 16% protein diets, enzyme levels were increased after 2 days rehabilitation and peaked after 5 days rehabilitation. The responsiveness of ODC to changes in dietary protein may be useful in the diagnosis of protein malnutrition.
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A deficiency of hepatic tyrosine aminotransferase in humans is responsible for a syndrome of keratitis, palmar and plantar erosions and hyperkeratosis and mental retardation. Serum tyrosine increases due to the enzymatic deficiency leads to the deposition of tyrosine crystals in the eye and cornea. This deposition and possible lysosomal activation leads to inflammation in the cornea and the skin. The syndrome can be reproduced in animals who are fed a high tyrosine diet. The interaction of tyrosine crystals with membrane-bound particles can be studied in vitro with lysosomes and erythrocytes.