Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potent skin tumor promoter (12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulates epidermal macromolecular synthesis as well as proliferation, but little is known of specific functional aberrations produced by TPA. This report presents results of a study on the effects of TPA on epidermal histidase (L-histidine ammonia lyase), an enzyme found in normal epidermis but not in dermis or in mouse squamous cell carcinomas. Histidase activity was assayed on postmitochondrial supernatants obtained from hairless mouse epidermis after removal by keratotome. Topical TPA treatment at doses active in tumor promotion (1.7 to 17.0 nmoles/application) produced dose-dependent decreases in epidermal histidase specific activity at 19 hr posttreatment. The onset of the decrease occurred at 12 hr with recovery to control level specific activity by 5 days, showing kinetics similar to those obtained for stimulation of DNA synthesis. This decrease in histidase could not be attributed to a general inhibition of soluble protein synthesis or to the appearance of an inhibitor of histidase activity. The strong promoter TPA produced a greater histidase decrease than did the moderate promoter and mitogen 12,13-didecanoyl phorbol at equimolar dose, while phorbol, a nonpromoter and nonmitogen, produced no effects on histidase. The relationship of this histidase depression to tumor promotion and not initiation is further indicated by the finding that (a) Tween 60, a structurally unrelated tumor promotor, also produced a decrease in histidase; and (b) the tumor initiator urethan and an initiating dose of 9,10-dimethybenz(a)anthracene showed no effects on histadase activity.
 ...
PMID:Decrease of epidermal histidase activity by tumor-promoting phorbol esters. 118 5

Histidine metabolism was studied in rats fed 10% casein diets supplemented with 1000 IU of retinol/g concurrent with or previous to exposure to high levels of dietary histidine (1% or 2%). When a retinol-supplemented 10% casein + 1% histidine diet was fed ad libitum for 21 days, urinary excretion of formiminoglutamic acid (FIGLU) was decreased by 50-70% over the entire period and plasma histidine was reduced by 30-70% for 16 days compared to rats receiving 10% casein + 1% histidine with normal levels of retinol. Rats pretreated for 10 days with a 10% casein diet supplemented with high levels of retinol oxidized 30% more L-[ring-2-14C]histidine to 14CO2 and excreted 76% less of the administered dose as urinary FIGLU compared to control rats not pretreated with high levels of retinol. Depression in growth due to supplementation of a 10% casein diet with 1% histidine were also partially alleviated in rats that were first pretreated with retinol. Activities of histidase, urocanase, and formiminoglutamic acid formiminotransferase (FIGLU transferase) were unaffected by retinol supplementation. The results suggest that retinol supplementation enhances histidine catabolism by exerting a change on one-carbon metabolism.
 ...
PMID:Enhancement of histidine and one-carbon metabolism in rats fed high levels of retinol. 612 Oct 19