PubMed · 3879735
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
P Esbrit, A Rapado. 1985. [Tumor hypercalcemia].. https://pubmed.ncbi.nlm.nih.gov/3879735/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Leukotriene (LT)C4 synthase is a membrane-bound, specific glutathione transferase which catalyzes the transformation of LTA4 to LTC4. It was originally shown to be present in rodent mastocytoma and basophilic leukemia cells as well as in macrophages. Recently, expression of human LTC4 synthase was demonstrated in platelets (Söderström, M., et al. (1992) Arch. Biochem. Biophys. 294, 70-74). The present report describes the induction of LTC4 synthase activity during differentiation of human erythroleukemia (HEL) cells by the protein kinase C stimulator 12-O-tetradecanoyl phorbol 13-acetate (TPA), ligands of the steroid-thyroid hormone receptor superfamily: all-trans-retinoic acid (RA) and 1 alpha, 25-dihydroxy-vitamin D3 and in addition dimethylsulfoxide (DMSO). TPA was the most powerful inducer of enzyme activity followed by 1 alpha, 25-dihydroxy-vitamin D3 and DMSO. RA did not induce LTC4 synthase activity.
Using new steroidal side-chain-lengthened 26,27-dialkyl analogues of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3], we manipulated the synthesis of thromboxane and thromboxane-producing enzymes, cyclo-oxygenase and thromboxane synthase, in human promyelocytic leukemia (HL-60) cells in serum-free culture. The order of potency of the analogues for stimulating thromboxane B2 synthetic activity from arachidonic acid (reflecting combined cyclo-oxygenase activity and thromboxane synthase activity) and from prostaglandin H2 (thromboxane synthase activity only) as well as for cyclo-oxygenase induction was 1 alpha,25-(OH)2D3 > or = 1 alpha,25-(OH)2-26,27-CH3)2D3 > 1 alpha,25-(OH)2-26,27-(C2H5)2D3 >> 1 alpha,25-(OH)2-26,27-(C3H7)2D3. These results suggest that there are functional and structural limits to the chain length of C-26 and C-27 dialkyl groups flanking the C-25-OH group in the 1 alpha,25-(OH)2D3 molecule for expressing thromboxane synthetic activity in HL-60 cells. Removal of the C-1 alpha-OH group from 1 alpha,25-(OH)2D3 led to markedly decreased thromboxane synthetic activity in HL-60 cells. These structure-activity relationships indicate that both the C-25-OH and C-1 alpha-OH groups in the 1 alpha,25-(OH)2D3 molecule are essential for expressing thromboxane synthesis in HL-60 cells. Also, the rank order for stimulating thromboxane synthesis correlated well with the binding affinity of these dialkyl analogues for the 1 alpha,25-(OH)2D3 receptor of HL-60 cells, suggesting a 1 alpha,25-(OH)2D3 receptor-mediated induction mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
The expression of the leukemia inhibitory factor/D factor (LIF) gene in human T-cell leukemia virus type 1 infected T-cell lines was examined. Human T-cell leukemia virus type 1 infected T-cell lines MT-1, MT-2, H89-59, H89-79, and H109 expressed LIF mRNA, but the T-cell lines MOLT-4 and TALL-1 did not. LIF mRNA expression was enhanced by interleukin 2 or 12-O-tetradecanoylphorbol-13-acetate in MT-2 cells. The biological activity of LIF was detected in culture medium enhanced by interleukin 2 in MT-2 cells. The expression of LIF mRNA was suppressed by 1 alpha,25-dihydroxyvitamin D3 and dexamethasone. These results imply that the expression of the LIF gene is involved in the development of hypercalcemia and abnormalities of the immune system observed in patients with adult T-cell leukemia.