The biological activity of all-trans retinol, in human keratinocytes, was investigated through metabolic and functional analyses that assessed the capacity for retinol uptake and metabolism and the mechanism of retinol-induced activation of gene transcription. Human keratinocytes converted all-trans retinol predominantly to retinyl esters, which accounted for 60 and 90% of cell-associated radio...

The kinetics and metabolism of physiological doses of all-trans-retinoic acid were examined in blood and small intestinal mucosa of vitamin A-depleted rats. A major portion of intrajugularly injected retinoic acid is rapidly (within 2 min) sequestered by tissues; subsequently 13-cis-retinoic acid and polar metabolites are released into circulation. All-trans-retinoic acid appears in small intes...

BACKGROUND The clinical activities of all-trans retinoic acid in the treatment of acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia, have triggered extensive studies aimed at defining the mechanisms by which this compound induces differentiation of leukemic cells. Recent studies show that hypoxia-inducible factor-1 alpha (HIF-1 alpha) contributes to the differentiation of...

The discovery of the biological activity of 9-cis-retinoic acid raises questions as to its mode of biosynthesis. A simple mechanism involves the direct isomerization of all-trans-retinoic acid to 9-cis-retinoic acid. It is shown here that bovine liver membranes, but not supernatant fractions, can isomerize all-trans-retinoic acid into 9-cis-retinoic acid and 13-cis-retinoic acid. The concentrat...

Hematology-Oncology Department Ospedali Riuniti Largo Barozzi, 1 24128 Bergamo (Italy) Tel. 39 035 269492, Fax 39 035 266659 E-Mail [email protected] All-trans-retinoic acid (ATRA) inhibits cell growth and proliferation by inducing cyto-differentiation and/or apoptosis in several cell types. These effects have become a therapeutic objective in human cancers. In addition to these functions, ...

The relationship between dietary vitamin A and all-trans-retinoic acid levels in serum and tissues had not been quantified. We determined the impact of dietary vitamin A on retinoid levels in serum, liver, kidney, testis, and epididymal white adipose of five mouse strains: AKR/J; BALB/cByJ; C3H/HeJ; C57BL/6J; 129S1/SvImJ. Retinoids were quantified in mice fed copious vitamin A (lab chow, ≥20 IU...